Management of HIV-related Conditions and Antiretroviral Therapy in Adults and Children

HIV Guide for Primary Health Care in South Africa

Seventh edition, October 2010

MEDECINS SANS FRONTIERES

Management of HIV-related Conditions and Antiretroviral Therapy in Adults and Children

HIV Guide for Primary Health Care in South Africa
Seventh edition, October 2010

Editors: Isabel Zuniga, Gilles van Cutsem and Peter Saranchuk Contributors: Musaed Abrahams, Funeka Bango, Martha Bedelu, Helen Bygrave, Sarah Christianson, Xavier Donceel, Elizabeth du Toit, Eric Goemaere, Katherine Hilderbrand, Washiefa Isaacs, Estelle Kastoor, Francoise Louis, Gcina Mahlangeni, Carolina Malavazzi Galvo, Nompumelelo Mantangana, Cheryl McDermid, Lucy Pamment, Tony Petter, Hermann Reuter, Peter Saranchuk, Nolitha Tsilana, Gilles Van Cutsem, Isabel Zuniga. Acknowledgments: This guide has only been possible with the support of numerous health care workers and patients from the Khayelitsha, Lusikisiki, and Morija programs. Design and layout: Designs4development, www.d4d.co.za Printing: RSA Litho Cover photo: Julie Rmy

Mdecins Sans Frontires Building 20, 303A&B, Waverley Business Park, Wyecroft Road, Mowbray, Cape Town, South Africa, 7925. Telephone: 021 448 1058 Town One Properties Site B, Sulani Drive, Khayelitsha 7784, Cape Town, South Africa www.msf.co.za Comments to be addressed to [email protected] 978-0-620-48827-3 First edition published 2001. Second edition published 2003. Third edition published 2005. Fourth edition published 2006. Fifth edition published 2007. Sixth edition published in 2009. Copyright 2010, Mdecins Sans Frontires. Any part of this material may be reproduced, copied or adapted, provided that the parts reproduced are free of charge, that the source is referenced and that notification is sent to Mdecins Sans Frontires. All material may only be used for not-for-profit purposes.

Dedicated to the memory of Dr. Sarah Ann Christianson (MacIntyre) May your energy and dedication shine through the pages of this book

The Medicines Information Center (MIC) has set up a toll-free hotline for any clinical and/or drug queries related to HIV/ART.

MIC HIV Toll-free Hotline: 0800 212 506

MIC email: [email protected]

HIV Guide for Primary Health Care

Foreword
This guide is designed to assist primary health care workers with decision-making in clinical management of HIV-related conditions in adults and children. This includes antiretroviral therapy and tuberculosis. The first edition was developed for use in primary health care level HIV clinics opened by Mdecins Sans Frontires (MSF) in the township of Khayelitsha, Cape Town, South Africa. It successfully became a practical reference tool for nurses and doctors in the clinics of Khayelitsha, and later in the MSF projects located in the rural areas of Lusikisiki in the Eastern Cape and Morija, Lesotho. We hope that this guide will be useful in other resource-limited settings as well. As larger numbers of patients were started on ARVs, it became increasingly clear that HIV/TB care had to be nurse-based and decentralized to the primary care level. This is reflected in South Africas National Strategic Plan for HIV & AIDS and STI, 2007-2011 (NSP) and the University of Cape Towns Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) health systems intervention. This guide aims to support the implementation of the NSP as well as STRETCH. It reflects the 2010 South African National ART guidelines, the 2009 National TB Management guidelines, and the 2008 Practical Approach to Lung Health and HIV/AIDS in South Africa (PALSAPlus) guidelines. We tried to keep the guide as simple and as accurate as possible. Although we consulted published literature during its compilation, there is certainly personal bias reflecting the authors views as well. By no means should this guide replace more detailed textbooks or clinical discussions. It is hoped that this seventh edition will continue to help nurses and other clinicians to prevent many unnecessary deaths from HIV and TB across southern Africa. The guide is a work-in-progress. Our current management strategies for HIV-related conditions will be confirmed or rejected by observational research in the future. We hope the reader will acknowledge this, and we would be grateful for any comments to make the next edition even better. Have a good read!

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Contents
page

xiii 1 3 4 5 7 8 8 8 9 10

Abbreviations Introduction Table 1: Risk of infections related to CD4 count Summary of Treatment Interventions Figure 1: Medical Treatment to prevent unnecessary death Epidemiology, Life Cycle, and Prevention of HIV Epidemiology of HIV HIV life cycle Figure 2: Life Cycle of HIV Prevention of HIV Accidental exposure of health care workers and Post-exposure prophylaxis (PEP) Assessment and Follow-up of the Patient First consultation Second consultation Further follow-up consultations Preventive therapy (also known as prophylaxis) Figure 3: INH prophylaxis (adults) Table 2: Cotrimoxazole prophylaxis Symptom Management Introduction: Summary of a Thorough Clinical Assessment Rash Difficulty swallowing Diarrhoea Abdominal pain Cough Fever Weight loss Algorithm 1: Investigation of Weight Loss Headache Algorithm 2: Investigation of Headache

13 14 15 16 18 20 21 23 24 24 24 25 25 25 25 28 30 31 33

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34 35 39 40 41 42 43 44 44 46 46 47 48 49 49 50 50 52 52 54 55 56 59 60 61 61 62 63 63 64 67 68 69

Confusion Lymphadenopathy Skin Conditions Algorithm 3: Diagnosis of Rash in an HIV Patient Xerosis Papular pruriginous eruption (PPE) Scabies Tinea pedis (Athletes foot) Tinea corporis (also known as Ringworm) or Tinea capitis Seborrheic dermatitis Nappy rash Herpes simplex (HSV) Molluscum contagiosum Warts (Human Papilloma Virus) Bacterial folliculitis Impetigo Herpes Zoster (Shingles) Varicella (Chickenpox) Kaposi Sarcoma (KS) Drug rash Psoriasis Bed sores Mouth Lesions Algorithm 4: Clinical management of Difficulty swallowing Oral health Oral candidiasis (oral thrush) Angular stomatitis (cheilitis) Aphthous ulcers (canker sores) Oral hairy leukoplakia (OHL) Oesophageal candidiasis (oesophageal thrush) Gastrointestinal Conditions Algorithm 5: Management of diarrhoea Acute diarrhoea

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71 74 75 75 79 80 81 83 86 87 88 88 89 90 91 92 95 96 98 99 103 104 105 107 108 109 111 112 114 115 117 117 118

Chronic diarrhoea Algorithm 6: Approach to abdominal pain Abdominal pain Hepatitis B co-infection Pulmonary Conditions Figure 4: Pulmonary conditions not to miss Introduction to pulmonary conditions Pulmonary tuberculosis (PTB) Algorithm 7: Smear-negative TB Table 3. Frequency of sputum/culture follow up for patients with TB Table 4. Regimen 1: New cases, > 8 years and adults Table 5. Regimen 2: Re-treatment cases, > 8 years and adults Table 6. Regimen 3: Children < 8 years Table 7. Changes to ARV regimen while on treatment for TB Table 8. Timing of ARV initiation after the start treatment for TB Special considerations in the TB-HIV co-infected child Prevention of TB Table 9: Dosage recommendations for INH preventitive therapy in children Algorithm 8: Screening of a child with documented TB exposure Drug resistant TB Bacterial pneumonia Table 10: Amoxicillin dose in children Pneumocystis jiroveci pneumonia (PCP) Table 11: High dose CTX (for PCP treatment only) Lymphoid interstitial pneumonia (LIP) Pulmonary Kaposi sarcoma Neurological Conditions Peripheral neuropathy Bacterial meningitis Cryptococcal meningitis TB meningitis (TBM) Cerebral toxoplasmosis HIV encephalopathy / dementia

HIV Guide for Primary Health Care

121 122 122 123 123 125 126 127 128 129 130 130 131 132 133 134 136 137 137 140 143 144 145 148 148 151 152 154 154 156 157

Psychiatric Conditions Depression Anxiety Psychosis Delirium Genital and Gynaecological Conditions Algorithm 9: Syndromic STI management (protocols 1, 2) Algorithm 10: Syndromic STI management (protocols 3, 4) Sexually transmitted infections (STIs) Table 12: Treatment of asymptomatic partners Protocol 1 (males): Urethral discharge or dysuria Protocol 2 (males or females): Genital ulcer syndrome (GUS) Protocol 3 (females): Vaginal discharge syndrome (VDS) Protocol 4 (females): Lower abdominal pain or cervical tenderness Vulvo-vaginal candidiasis (vaginal thrush) Human Papilloma Virus (HPV) infection (Genital warts) Table 13: Cervical screening Syphilis Sexual assault Algorithm 11: Management of sexual assault Pregnancy And Children Algorithm 12: Management of pregnant women (+ PMTCT) HIV in pregnancy (including PMTCT) Table 14: NVP Infant Dosing Guide HIV in children Algorithm 13: Management of HIV-exposed babies Assessment and follow-up of HIV-exposed and infected children Table 15. Developmental checklist Table 16. Developmental warning signs Table 17. Cotrimoxazole prophylaxis dose Infant feeding

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161 162 162 164 169 170 170 171 172 173 173 174 174 175 175 175 177 178 178 178 179 180 180 183 184 185 185 186 186 187

Antiretrovirals (Arvs) Perspective Principles of therapy with ARVs Monitoring on ARVs Algorithm 14: Viral load monitoring and switch to 2nd line Second line treatment in adults Criteria for switching to 2nd line treatment in children (SA) Side effects of ARVs Algorithm 15: Managing ARV side effects Nausea +/- vomiting Rash Dizziness Peripheral neuropathy Hepatitis Pancreatitis High lactate / lactic acidosis Algorithm 16: Management of lactic acidosis Lipodystrophy Hyperglycaemia Hyperlipidemia Immune Reconstitution Inflammatory Syndrome (IRIS) Drug interactions Conclusion Management of Pain Figure 5: Pain management (Pain ladder) General introduction to pain Management steps (WHO) Table 18. Paracetamol: childrens dose Table 19. Paracetamol and codeine: childrens dose Neuropathic pain Appendices

190 192 194

Appendix 1: WHO Clinical Staging of HIV Infection in Adults Appendix 2: WHO Clinical Staging of HIV/AIDS for infants and children Appendix 3: Enrolment Criteria for ARVs in Adults

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200 200 203 205 207 211 216 219 221 223 230 231 232 233 234 238 239 241 243 244 249 251 257 259 260 262 264 266 268

Appendix 4: Enrolment Criteria for ARVs in Children Table 21: SA ART eligibility criteria for HIV-infected children (2010) Appendix 5: ARVs: Different Classes and General Rules Appendix 6: The Antiretrovirals (ARVs): Availability & specifics Appendix 7: Typical ARV regimens for adults Appendix 8: ARV regimens for children Appendix 9: Antiretroviral drug dosing chart for children Appendix 10: Monitoring a Patient on ARVs Appendix 11: Early and late side effects of ARVs Appendix 12: Grading and management of side effects Appendix 13: Common drug interactions Appendix 14: Key points for clinical review of systems & signs Appendix 15: Karnofsky Performance Score Appendix 16: Desensitisation with cotrimoxazole Appendix 17: Introduction to interpretation of blood results Appendix 18: Safe preparation of formula milk Appendix 19: Disclosure to children Appendix 20: Collecting a good sputum sample Appendix 21: Building a DR TB treatment regimen Appendix 22: DR TB Monitoring Appendix 23: Ishihara test for colour blindness Appendix 24: Management of Adverse Effects of DR TB treatment Appendix 25: Dosages of DR TB Drugs Appendix 26: PMTCT in late presenters (after 72 hours of life) Appendix 27: Common, serious chest x-ray finding in PLWHA Appendix 28: Common, serious retinal findings in PLWHA Appendix 29: Fine needle aspiration biopsy Appendix 30: Dose adjustments of drugs in case of renal failure Index

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Abbreviations
3TC ABC ADA AFASS AFB AIDS ALT ART ARVs ASAP ATV AZT BCG BD BMI BSA CrCl CMV CNS CRP CTX CXR D4T DDI DR TB EFV EPTB FBC FTC HAART Hb HBsAg HBV HCW HIV HSR HSV IM IMCI INH IRIS IV Lamivudine Abacavir Adenosine deaminase (a test done on pleural fluid to detect TB) Affordable, feasible, accessible, safe and sustainable Acid-fast bacilli (the tuberculosis germ) Acquired Immunodeficiency Syndrome Alanine aminotransferase (a liver blood test) Antiretroviral therapy Antiretrovirals As soon as possible! Atazanavir Zidovudine (occasionally also written as ZDV) Bacillus Calmette-Gurin Twice daily Body mass index (used to classify adults as overweight or underweight) Body surface area (sometimes used to calculate ARV dosages in children) Creatinine Clearance (a measure of kidney function) Cytomegalovirus Central Nervous System C-reactive protein (a blood test that measures inflammation) Cotrimoxazole (Bactrim, Cotrim, Purbac or Cozole) Chest X-ray Stavudine Didanosine Drug resistant TB (used in this guide to mean at least rifampicin resistance) Efavirenz Extra-pulmonary tuberculosis (TB outside of the lungs) Full Blood Count Emtricitabine Highly Active Antiretroviral Therapy Haemoglobin Hepatitis B surface Antigen Hepatitis B Virus Health care worker Human Immunodeficiency Virus Hypersensitivity reaction Herpes Simplex Virus Intramuscular Integrated Management of Childhood Illnesses Isoniazid (one of the TB drugs) Immune Reconstitution Inflammatory Syndrome Intravenous (same as drip)

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HIV Guide for Primary Health Care

KS LFT LP LPV/r MAC MDR TB MSF MTCT NB NNRTI NRTI NTM NVP OI ORS PCP PEP PCR PI PID PLWHA PMTCT PN PPD PPE PRN Pt. PTB QID RPR RTV SCC STI TB TBM TDF TDS TST UTI VDRL WHO XDR TB

Kaposi Sarcoma (a cancer) Liver Function Test Lumbar puncture (to diagnose meningitis) Lopinavir/ritonavir (Kaletra or Aluvia) Mycobacterium Avium Complex Multi-drug resistant tuberculosis Mdecins Sans Frontires (French for doctors without borders) Maternal to child transmission Note Bene in Latin, meaning note well or, pay special attention to the following Non-nucleoside Reverse Transcriptase Inhibitor (Non-nukes) Nucleoside Reverse Transcriptase Inhibitor (Nukes) Non-tuberculous Mycobacteria Nevirapine Opportunistic Infection Oral Rehydration Solution Pneumocystis jiroveci Pneumonia (a life-threatening OI) Post-exposure Prophylaxis Polymerase Chain Reaction (a laboratory test) Protease Inhibitor Pelvic Inflammatory Disease Person living with HIV/AIDS Prevention of Mother-to-Child Transmission (of HIV) Peripheral neuropathy Purified protein derivative (used in TB skin testing) Papular pruriginous eruption (a common itchy rash) As required Patient Pulmonary Tuberculosis (TB of the lungs) Four times a day A test for syphilis Ritonavir Smear and culture control Sexually Transmitted Infection Tuberculosis Tuberculous Meningitis Tenofovir Three times a day TB skin testing Urinary Tract Infection A test for syphilis World Health Organization Extensively drug-resistant tuberculosis

Introduction

Introduction
1. We are living in the age of HIV. Within a few decades, this virus has caused an enormous amount of morbidity and mortality around the world. Countries in southern Africa have been particularly hard hit. 2. Unfortunately, there is still an enormous amount of fear and stigma surrounding HIV, AIDS, and TB. This is made worse by a general lack of knowledge about these diseases, even among health care professionals. 3. Following infection, HIV slowly makes a persons immune system weak over many years. This progressive immunodeficiency roughly correlates with a gradual drop in the CD4 cell count (test), a type of white blood cell. As the CD4 count drops, certain infections and other illnesses are more likely to appear (see Table 1 on page 3). 4. As their immune systems weaken and they suffer from more frequent and severe infections (and cancers), we classify adults and children into different Clinical Stages of HIV infection. The WHO Classifications (see Appendices 1 & 2) are valuable tools in our clinics; all health care professionals (and patients) should be knowledgeable about the different stages of HIV! 5. Without comprehensive medical care, HIV-positive adults and children ultimately die from serious infections (or cancers). Fortunately, certain medical interventions now widely available can prevent many of these deaths (see pages 4 and 5). The medical interventions required for those in the final stages of HIV infection (suffering from recurrent life-threatening infections) are intense, while those in the initial stages of HIV infection need mainly psychological support and counselling. 6. Good nutrition is important at every stage of HIV infection. A healthy balanced diet together with supplementation of certain micronutrients (vitamins and minerals) help to delay disease progression from stage 1 to 4 (AIDS). It is important to note that nutrition alone in the final stages of HIV infection is not enough to prevent death! 7. Early recognition and treatment of Opportunistic Infections (OIs) is vital. People do not die from HIV; they die from infections (and sometimes cancers). If we diagnose these conditions early, and give proper medical treatment, we can avert many deaths. EARLY recognition of tuberculosis (TB) is especially important. 8. Proper medical care in the later stages also includes prevention of serious infections (also known as prophylaxis). Never forget to give regular preventive

HIV Guide for Primary Health Care

doses of the antibiotic cotrimoxazole to adults or children in the later stages of HIV infection (see Table 2 on page 21). Some individuals may also benefit from isoniazid prophylaxis to help prevent TB. 9. When an HIV-positive persons immune system has become too weak, we use antiretrovirals (ARVs) to stop HIV from growing, which in turn allows the immune system to recover. This is how ARVs prevent unnecessary death in patients with advanced HIV infection. Note that only those adults and older children in the later stages of HIV infection need ARVs. For HIV positive infants, early treatment regardless of clinical or immunological stage has proved to be beneficial (with a 75% reduction in mortality in a South African study-known as CHER study). 10. ARVs are not perfect. Just like all other medications, they have possible side effects. We must monitor people on ARVs closely in order to detect serious side effects early, and then make necessary changes.

Introduction

Table 1: Risk of Opportunistic Infections (OIs) and other HIV-related Conditions by CD4 cell count
CD4 count Any CD4 count Condition Persistent generalised lymphadenopathy (PGL) Salivary gland enlargement Herpes Zoster (Shingles) Tuberculosis Bacterial pneumonia Cervical intraepithelial neoplasia (CIN) Vulvo-vaginal candidiasis Chronic anaemia HIV-related thrombocytopenia Lymphocytic Interstitial Pneumonitis (LIP, commonly seen in children) < 200 cells/L (when severe OIs begin to appear) Oral candidiasis (I.e. thrush) Oesophageal candidiasis Oral hairy leukoplakia (OHL) Pneumocystis jiroveci Pneumonia (PCP) Cryptosporidiosis Lymphoma (non-CNS) Kaposi Sarcoma (KS) HIV-associated Dementia < 100 cells/L Toxoplasmosis Cryptococcal meningitis (CCM) Cytomegalovirus infection (Eye) Wasting Syndrome < 50 cells/L Non-tuberculosis mycobacterial (NTM) infection Lymphoma (CNS) Progressive multifocal leukoencephalopathy (PML) Cytomegalovirus infection (brain or disseminated)

HIV Guide for Primary Health Care

Summary of Treatment Interventions used to Prevent Death from HIV/AIDS

1. Early VCT in order to know ones HIV status early so that treatment interventions can take place early! 2. Counselling in order to allow a person to accept being HIV-positive. 3. Education about the HIV life-cycle, the different clinical stages of HIV infection, and CD4 counts. Counselling about possible OIs and sexual health. 4. Good nutrition, first a healthy diet, but if possible also includes supplementation with micronutrients (vitamins and minerals). 5. Early diagnosis and prompt treatment of opportunistic infections (OIs), especially TB. 6. Prevention of OIs with cotrimoxazole (and other medications) and prevention of TB with INH prophylaxis. 7. Antiretrovirals (ARVs) to lower the HIV viral load and allow a persons immune system to recover. 8. Monitoring for any side effects of ARVs in the short-term and the long-term. 9. Prevention of transmission of HIV, including transmission from mother to child (with PMTCT). 10. Ongoing adherence counselling and support, including support groups. 11. Monitoring for resistance that HIV can develop against ARVs.

Introduction

Figure 1: Patient Handout describing medical treatment to

Stage 1 2 Typical Symptoms None Person feels well Minor infections - rashes - shingles Early stage 3 More serious infections - TB in the lungs - frequent diarrhoea Weight Loss Late stage 3 and stage 4 (CD4 count usually <200 but could be >200) Severe weight loss Life-threatening infections - severe pneumonias - TB outside of the lungs - meningitis Cancers Get an HIV test done if you dont know your status! If you are HIV-positive, then Good nutrition, cotrimoxazole, education on TB & HIV and Antiretrovirals (ARVs) Treatment Good nutrition, exercise, accept your status, check CD4 regularly Good nutrition, exercise, learn the difference between HIV and AIDS, education on HIV & TB, regular check of CD4

prevent unnecessary death of people living with HIV and AIDS

Good nutrition, education on TB & HIV Cotrimoxazole and isoniazid to prevent new infections

visit your clinic to get a blood test to find out your CD4 count! If your CD4 count is less than 200, then your immune system is very weak. You will need ARVs to prevent life-threatening infection.

HIV Guide for Primary Health Care

HIV Guide for Primary Health Care

Epidemiology, Life Cycle and Prevention of HIV

Eva-Lotta Jansson

Epidemiology, Life Cycle and Prevention of HIV

Epidemiology of HIV
Countries in sub-saharan Africa have been hardest hit by the global HIV epidemic. As of 2008 in South Africa alone, an estimated 2.5 million people have already died from AIDS. Other S.A. estimates suggest that almost 1500 people are newly infected with HIV each day, resulting in almost 1 in 5 adults currently being infected (adult prevalence = 18.1%). In addition, almost 175 babies are newly infected with HIV each day in this country. The majority of people acquire HIV: Through sexual contact Before birth or during delivery Through breastfeeding Through using contaminated needles Through blood or blood products (rare when donor blood is carefully screened)

HIV lifecycle
There are at least 6 important phases that HIV must go through before new HIV can be produced. These are: 1. Attachment: HIV attaches to the CD4 (and CCR5/CXCR4) receptors of the cell 2. Fusion: HIV fuses with the cell-wall and enters the cell

Figure 2: Life Cycle of HIV

HIV particle HIV binds to host cell New viral particles

CCR5

Infected cell

gp120 CD4 HIV RNA Reverse transcription Integrase DNA copy of HIV RNA DNA Integrates

Protease

HIV particle budding from cell

Source: http://www.lifewins.co.za

HIV proteins RNA genomes

3. Reverse transcription: Viral RNA is transformed into viral DNA by an enzyme called reverse transcriptase (The drug classes known as NRTIs and NNRTIs act at this level by preventing this process). 4. Integration: Inside the nucleus of the CD4 cell, viral DNA is integrated into the cells genome, and then new material to form individual HIVs is made. 5. Protein production and protease function: Large proteins are broken into smaller proteins to become functional; Protease Inhibitors act at this stage. 6. Maturation: The final process during which new HIV viruses are released.
Epidemiology

Prevention of HIV
Primary prevention
Effective practices to reduce transmission of HIV are: Barrier methods: condoms! Safer sexual practices: delay sexual debut, reduce concurrent partners... Treating STIs Male circumcision Prevention of mother to child transmission (PMTCT), including infant ARV prophylaxis throughout the breastfeeding period. Provision of safe formula feeding Needle and syringes exchange programs Screening blood donors and testing blood products Post exposure prophylaxis (PEP) for health care workers and rape victims

Secondary prevention
Secondary prevention refers to practices that can help an HIV positive person stay well for as long as possible. These include: Going for regular clinic check-ups Eating a balanced diet and exercising regularly Taking preventive drugs such as cotrimoxazole or INH Starting ARVs early

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Epidemiology, Life Cycle and Prevention of HIV

Accidental exposure of health care workers and Post-Exposure Prophylaxis (PEP)

Ways in which exposure occurs
Health care workers are at risk of accidental exposure to blood or other body fluids through: Percutaneous injury with a needle or another sharp instrument. Exposure to blood or body fluids via mucous membranes (eye, mouth) or nonintact skin (wound, dermatitis, abrasion)

What to do in case of occupational exposure

If an occupational exposure happens to you or to one of your colleagues, treat this as an emergency: Immediately let the wound bleed (without scrubbing), wash both the wound and surrounding skin with water and soap (without scrubbing) and then rinse; Disinfect the wound and surrounding skin with: Povidone iodine 2.5 % (Betadine) during 5 minutes, or Alcohol 70% during 3 minutes

If you received an exposure involving the eyes or mucous membranes: rinse the exposed area immediately with as isotonic saline solution during 10 minutes. Antiseptic eye drops can also be used for eye exposure. If none of these solutions are available, use clean water.

Start Post-exposure prophylaxis (PEP) as soon as possible (ideally within 1 or 2 hours, not later than 72 hours after exposure). Give Zidovudine (AZT) + Lamivudine (3TC) + Lopinavir/ritonavir (LPV/r). A good alternative regimen is Tenofovir (TDF)/3TC + LPV/r. Those regimens will be taken for 1 month.

Notify your supervisor and/or a medical doctor.

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Notes
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Epidemiology

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Epidemiology, Life Cycle and Prevention of HIV

Notes
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Assessment and Follow-Up

Mariella Furrer

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Assessment and Follow-Up

First consultation
History
hief Complaint (the main problem today) C History of the Present Illness Past History Tuberculosis (TB) past history and/or recent TB contacts Other conditions, e.g. diabetes, hypertension, rheumatoid arthritis Psychiatric history Any other infections: shingles, thrush, chronic diarrhoea Weight loss Prior exposure to any ARVs (including PMTCT) Allergies (e.g. to cotrimoxazole)

Family History: Children? Partner? All tested? Any on treatment? Social History: Employment status and source of income Psychological support Disclosure of HIV status and outcome of the disclosure Alcohol / drug history

Review of Systems: Refer to Appendix 14 Identify any recent weight loss Screen for symptoms of STIs Screen for symptoms of TB

Physical examination
oes this person look stable or unstable? (If unstable, you will have to spend D more time with this person +/- refer to hospital.) Vital signs (heart rate, respiratory rate, blood pressure, temperature). Check weight and height at first visit and calculate Body Mass Index (BMI = W/H, where Weight is in kg and Height is in meters) A thorough systems examination to exclude OIs

Investigations
ake blood for CD4 at first visit or next specimen collection day. T

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Diagnosis
ist any OIs which are present L
Assessment and Follow-Up

Clinical staging
tage the patient following the SA-adapted WHO staging system (see S Appendices 1 and 2) Staging gives an idea of how sick a PLWHA has ever been. The stage can increase with new, more serious HIV-related conditions, but cannot decrease, even with improved health after ART initiation.

Treatment
reat any opportunistic infections (OIs) T Refer to a doctor if severely ill or in doubt Treat any STIs Prescribe cotrimoxazole for prevention of OIs if Stage 2, 3 or 4 or CD4<200 (adults). See Table 2 for criteria to start and stop CTX for children and adults. Ensure adequate nutrition (advice on diet and supplementation with vitamins) and, provide nutritional supplements if wasted or BMI < 18.5.

Counselling
eassure that infection with HIV is a treatable condition (not a death R sentence!) Importance of regular follow-up and benefit of prophylaxis and treatment Counselling on family planning and condom use (male and female) Encourage the client to have just one partner and encourage the partner to get tested for HIV If client will start ARVs: Explain that unsafe sex on ARVs can still transmit HIV which can lead to treatment failure.

Second consultation
Review of symptoms
ollow up on OIs and/or TB Symptoms. Educate client to return early if F symptoms develop.

Physical examination
oes this person look stable or unstable? (If unstable, you will have to spend D more time with this person +/- refer to hospital.) Vital signs if necessary Check weight (at every visit)

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Assessment and Follow-Up

Thorough examination to exclude new OIs and TB If the CD4 count is < 100 cells/L, perform a retinal examination through dilated pupils (to look for signs of TB, Toxo, CMV, etc)

Baseline blood tests

Hb (or FBC if available) CD4 count if not done at first consultation Consider screening for syphilis (VDRL or RPR testing) If eligible for ART perform baseline bloods for regimen of choice (See also Appendix 10 on page 219) Creatinine for TDF, FBC + differential for AZT, ALT for NVP Baseline viral load (for children < 15 years only) Consider checking for HBsAg if baseline ALT > 40 IU/ml (since important to be aware of Hepatitis B status in case TDF and/or 3TC will be stopped any time in the future)

Treatment
f taking CTX and/or INH, check adherence and tolerance I Treat any opportunistic infection

Counselling
he patient is encouraged to ask questions. T Counselling on the use of condoms is provided again. Follow-up appointment to be given to discuss lab results (within 1 week if sick, within 2 weeks if stable).

Further follow-up consultations

Clinical follow up
See above Remember to check weight at every visit Screen for pregnancy Perform or refer women for a PAP smear if one was not done during the last year; PAP smears should then be repeated every 3 years (even if previous ones were normal). If the patient is on TB therapy, sputum should be sent off at 2 and 5 months (3 and 7 months in TB retreatment cases). Screen household contacts of PTB patients looking for:

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ymptomatic or S < 5 years or HIV positive

Assessment and Follow-Up

Treatment and counselling

aboratory results are discussed. L Prevent OIs with cotrimoxazole if not already started (see Table 2, page 21, for indications). Prevent TB by means of INH prophylaxis, if clinically indicated (see Figure 3, page 20). If the adult (Appendix 3) or child (Appendix 4) is eligible for ART, refer for counseling about ARVs. Note that certain patients should be fast-tracked to initiate ART within 2 weeks.
Require fast track (i.e. ART initiation within 2 weeks of being eligible)

Pregnant women eligible for lifelong ART OR Patients with very low CD4 (< 100 cells/L) OR Stage 4, CD4 count not yet available OR MDR/XDR TB Children younger than 1 year

The patient is advised to bring a person they can trust (treatment assistant) so that both can receive any necessary counselling (and education about ARVs if eligible).

If the patient is on TB therapy, check the TB card to ensure that the person is adhering to treatment, that follow-up sputa have been taken and that culture and sensitivity results are available if taken.

Do not interrupt ARVs if TB is diagnosed. Refer to doctor if any complication develops after starting TB treatment. Smoking worsens TB treatment outcomes. Urge client to stop. Discuss plans for future pregnancies. Efavirenz may cause birth defects if taken in the 1st trimester (but is considered safe in the 2nd and 3rd trimesters). All women of childbearing age should receive nevirapine, or if on efavirenz, use reliable contraception.

Recent changes, including changes in residence, telephone numbers, surnames, new sexual partners and disclosure(s) need to be explored.

REMEMBER

The weight should be checked at every visit!

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Assessment and Follow-Up

Frequency of follow-up visits

The frequency of follow-up visits depends on the clinical stage and CD4 count: f the patient is eligible for ART*, especially if unstable, ensure weekly I assessment and management until started on ARVs. If patient is eligible for ART, refer for counseling about ARVs. If not eligible for ART, the person still requires regular follow-up, including advice on HIV prevention, INH prophylaxis, contraceptive advice, and routine Pap smears. CD4 testing should be repeated every 6 months. Even if not yet eligible for ART, every person must know to seek medical advice if they get sick in the interim. Frequency of CD4 testing in South Africa: If the patient is not yet eligible for ARVs: repeat 6 monthly On ARVs: At month 6, month 12, then annually (with viral load)

REMEMBER Check viral load at 6 months, 12 months, and

then every 12 months in patients on ARVs.
A viral load which is not lower than detectable limits (LDL) warrants an urgent visit to the counsellor to investigate reasons for virological failure.

O.I. Preventive therapy (also known as Prophylaxis)

Prevention (or prophylaxis) refers to medication given to prevent an infection from happening in the first place. We give cotrimoxazole to many HIV-infected people when they first come to our clinics as primary prevention against Pneumocystis pneumonia (PCP), cerebral toxoplasmosis and other infections (see Table 2 on page 21 and Table 17 on page 156). Note that primary prevention is different from secondary prevention. Secondary prevention means preventive measures given after a person has already suffered from a certain infection, in order to prevent that same infection from coming back again.

* The ART eligibility criteria from the 2010 S.A. Guidelines can be found on page 198 in Appendix 3 (adults) and page 200 in Appendix 4 (children).

19

Medication used for primary prophylaxis

otrimoxazole to prevent PCP or Toxoplasmosis for the first time C INH to prevent TB for the first time (see Figure 3 on next page)
Assessment and Follow-Up

Medication used for secondary prophylaxis

otrimoxazole to prevent recurrence of PCP or Toxoplasmosis C Fluconazole to prevent recurrence of Cryptococcal disease

INH to prevent recurrence of TB (see Figure 3 on next page) Both primary and secondary prophylaxis can be discontinued in a person on ARVs when the immune system has sufficiently recovered. See Table 2 on page 21 and sections on PCP, Cryptococcal meningitis, and Cerebral Toxoplasmosis for when to stop primary and secondary CTX prophylaxis.

20

Assessment and Follow-Up

Figure 3: INH Prophylaxis (Adults)

6 months of isoniazid (INH) protects against TB for 1824 months in PLWHA but you must exclude active TB first. Avoid INH prophylaxis in those on ARVs or about to start, and those having liver disease or abusing alcohol.

NO

Are there any symptoms of active TB? Cough > 2 weeks

YES

Prescribe: INH 300 mg daily + pyridoxine 25 mg daily for six months

Weight loss > 1.5 kg in 4 weeks Drenching night sweats Chest pain +/- bloody sputum Feeling unwell Lymph node > 2 cm

Investigate for TB sputum microscopy TB culture CXR +/- other investigations

NOTES:
Although not recommended in the S.A. guidelines, TB skin testing is performed in other settings and INH given only to those adults having a positive test result. Pregnancy is not a contra-indication to INH prophylaxis Interrupt INH prophylaxis if adherence is a concern and in case of severe PN or hepatitis (ALT > 5 times the upper limit of normality) See page 96 for INH prophylaxis in children

How to do a TB skin test (TST)? Keep PPD refrigerated (discard if open >8 hours or expired) Ensure client can return 4872 hours after test for reading. If not, reschedule test. Use 2 units of PPD-RT23 or 5 units of PPD-S. Locate area for injection (palm surface of left arm 48 cm below the elbow). Clean the area with an alcohol swab. Pull the skin taut. Using a tuberculin syringe, inject PPD into the layers to see a weal developing. Measure swelling/induration after 4872 hours If induration 5 mm in an HIV-positive person, TST is considered positive.

Table 2: Cotrimoxazole prophylaxis (also see Appendix 16 for desensitization schedule)

Indications to discontinue HIV-infected adults On ARVs and CD4 > 200 cells/ L on 2 consecutive occasions 3-6 months apart. HIV-exposed infant Negative PCR or rapid HIV test at least 6 weeks after complete breastfeeding cessation and absence of clinical signs of HIV infection. Non-severe side effects (grade 1 and 2): Desensitize adults (see Appendix 16) Desensitization should not be done in children If allergy or intolerance to cotrimoxazole

Recommended dose/ Protection against

Indications to start

Recommended dose Adults: CTX 480 mg, 2 tablets daily

HIV-infected adults CD4 < 200 cells/L or clinical stages 2, 3 or 4

Infants and children: dosage according to body weight (see Table 17 on page 156)

All HIV-exposed infants Starting at 6 weeks of age

If taken regularly, CTX protects against Pneumonia, especially PCP HIV-infected children without previous PCP or toxoplasmosis*: < 12 months: Dont stop 1-5 years: On ARVs and CD4 > 15% (or > 500 cells/ L) on 2 consecutive occasions 3-6 months apart. >= 6 years: On ARVs and CD4 > 15% (or > 200 cells/L) on 2 consecutive occasions 3-6 months apart.

HIV-infected children Under 1 year: All

Grade 3 toxicity to CTX or desensitization not successful: Dapsone 100 mg daily (protects against PCP, but limited protection against toxoplasmosis)

Brain infections (toxoplasmosis)

Certain types of diarrhea

1-5 years: stages 2, 3 or 4, or CD4 <15% (or < 500 cells/ L)

Therefore, add Pyrimethamine 50 mg + Folinic acid** 25 mg weekly to protect against Toxoplasmosis if available

Other bacterial infections, such as UTI

Malaria

>= 6 years: stages 3 or 4, or CD4 < 200 cells/ L

In case of severe reactions to CTX (grade 4 skin, liver, kidney or bone marrow toxicity), Dapsone should not be used, as there may be cross-reactivity Dapsone is safe in pregnancy Dapsone (2mg/kg/day) can be given to infants and children unable to tolerate CTX
** Note that Folinic acid is not the same as Folic acid!

HIV-infected children with previous PCP or toxoplasmosis*: < 6 years: Dont stop >= 6 years: On ARVs and CD4 > 15% (or > 200 cells) on 2 consecutive occasions 3-6 months apart.

CTX is a combination of two antibiotics: Trimethoprim (TMP) and Sulfamethoxazole (SMX)

There are several trade names for CTX: Bactrim, Septrim, etc.

* Children at risk of malaria should be maintained on CTX until that risk subsides

21

Assessment and Follow-Up

22

Assessment and Follow-Up

Notes
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Symptom Management

Alessandra Vilas Boas

24

Symptom Management

Introduction
Patients do not present complaining of a diagnosis (such as TB meningitis). Rather, they come to us with symptoms (such as headache or confusion). We must take a good history of the presenting symptoms, perform a proper physical examination, and come up with the diagnosis (with the help of investigations). Only then can we make a treatment plan that will make this patient better. See Appendix 14 for key points for clinical review of symptoms and signs.

REMEMBER

Summary of a Thorough Clinical Assessment (Also see First Consultation on page 14):

It is very important to be thorough when dealing with HIV patients: 1. Take a good history. 2. Perform a good physical examination. 3. Do any necessary investigations. 4. Come up with a diagnosis, including the Clinical Stage of HIV Infection. 5. Arrange a treatment plan that will make the patient better. 6. Dont forget to prescribe prevention treatment (cotrimoxazole or other). The following serious symptoms can be caused by OIs that commonly occur in HIV-positive patients. They require a thorough clinical assessment in order to arrive at the correct diagnosis (and subsequent treatment plan).

Rash
See the algorithm on page 40 and the text in the following pages for a practical approach to the most common causes of skin rash and their management. Rash is very common in patients with HIV. Patients presenting with rash should always be advised to test for HIV. Of particular importance is to recognize life-threatening skin rashes such as Kaposi sarcoma and severe drug eruptions (Stevens Johnsons syndrome).

Difficulty swallowing
An approach to difficulty swallowing can be found on page 60. In patients with low CD4 counts, oesophageal candidiasis is the most common cause of difficulty swallowing. This is a stage 4 defining illness and an indication for urgent treatment and urgent ART. Alternative diagnoses include herpes simplex, aphthous ulcers and CMV ulcers. In early HIV, gastro-oesophageal reflux disease (GERD) is a common cause.

25

Diarrhoea
See page 68 for diagnosis and management. Diarrhoea can cause severe loss of weight and be very debilitating. It is important to distinguish between acute and chronic diarrhoea. Whilst acute diarrhoea can occur at any stage of HIV, chronic diarrhoea is a sign of advanced disease and an indication to start ART.
Symptom Management

Abdominal pain
See page 7475 for algorithm and management. Some differential diagnoses not to be missed are: abdominal TB, acute hepatitis (viral or drug related), gastric ulcers, pelvic inflammatory disease, appendicitis, and pancreatitis.

Cough
See page 80 for an approach to cough and the most common respiratory diseases. Remember that TB is the first cause of death among patients with HIV. A screening for TB should happen at every consultation.

Fever
High temperature (also known as pyrexia or fever) is common in HIV-positive patients. HIV itself can cause high temperature, as can numerous infections. It is very important to rule out infection first as the cause of the high temperature, before blaming the fever on HIV, since there is a risk of death from many infections if they go undiagnosed (HIV-positive patients die mainly from infections, not from HIV itself!).

Causes
Causes of high temperature include: ll types of infections: Those related to HIV (opportunistic infections) and those A not necessarily related to HIV Some cancers (especially Non-Hodgkins Lymphoma) Life-threatening infections (rule these out first) Tuberculosis Other lung infections Acute diarrhoea causing dehydration Sepsis Meningitis

26

Symptom Management

Other infections such as STIs (PID) Certain medications can cause a fever (this is called a drug fever). However, drug fever is a diagnosis of exclusion (meaning that infections must be ruled out first).

Clinical history (see also Appendix 14)

A thorough clinical history is essential to help identify any fever due to infection. Some important symptoms to ask about include: ore throat (suggests pharyngitis or throat infection) S Facial pain with post-nasal drip (suggests sinusitis) Headache (need to rule out meningitis) Dysuria or painful urination (check for UTI) Diarrhoea (see pages 6873) Abdominal pain (see Algorithm 6 on page 74) Pelvic mass (perform urine pregnancy test) Cough (check for pneumonia and investigate for TB) Night sweats and loss of weight (check for TB without delay) Dyspnoea (check for PCP or other chest infection and refer to doctor) Enlarged nodes (if not responding to antibiotics, its probably TB, but also consider lymphoma) Seizures (refer to doctor)

Clinical examination (see also Appendix 14)

A thorough clinical examination to help identify the cause of the fever must include: eight W Vital signs (I.e. BP, pulse, temp, and respiratory rate) Signs of dehydration +/- shock Assessment of vision, including retinal examination Examine ears, mouth, throat and sinuses Check for neck stiffness Listen to chest to check for crackles, wheezing, pleuritic rub Listen for a heart murmur Look for enlarged lymph nodes in neck, armpits and groin Abdominal tenderness, mass, or loss of bowel sounds Liver and/or spleen enlargement

27

Examine skin for any infected rashes (or oozing sores) Examine for focal signs (such as new-onset weakness of an arm and/or leg)

Investigations
Perform investigations as necessary: rinalysis for blood, protein, and leukocytes U Urine test for pregnancy Chest X-ray If TB suspected, sputum examination for AFB +/- TB culture FBC + differential cell count Referral for LP (if meningitis suspected)
Symptom Management

Management
Specific treatment depends on the results of the history, examination, and investigations. Always treat the underlying cause of the infection! Ensure adequate fluid intake. Unless a virus (such as the flu) is suspected as the cause of the high temperature, the patient will usually need treatment with an antibiotic, even when waiting for test results (for example, Amoxicillin for chest infection while waiting for TB smear results). Refer to the doctor if the patient is very sick or if in doubt about the cause of the fever. The following medications can help lower a high temperature and provide some relief, but they do not treat the infection: Paracetamol 500-1000 mg four times daily as required for adults Ibuprofen 200-400 mg four times daily as required for adults Paracetamol syrup four times daily as required for children, depending on weight (see Table 18 on page 186) Make sure that patients understand they must return for reassessment if there is no improvement, or they are getting worse.

28

Symptom Management

Weight loss
Weight loss is very common in HIV-infected people. It can be due to HIV itself known as HIV wasting syndrome, which is an AIDS-defining condition (I.e. clinical stage 4) requiring ART. HIV wasting syndrome is defined as unexplained weight loss (> 10% of baseline body weight) with obvious wasting or BMI < 18.5, plus unexplained diarrhea and/or fever for > one month. However, wasting is a diagnosis of exclusion. More commonly, it is due to infections that cause loss of appetite (E.g. TB) or decreased absorption of nutrients (chronic diarrhoea). After initiation of ARVs, weight loss can also represent a side effect of ARVs (for example, high lactate levels due to D4T). Documented weight loss of > 1.5 kg over 4 weeks should be regarded as significant and must be investigated. If the client is not yet on ARVs and presents with HIV wasting syndrome, fast-track for ART initiation regardless of CD4 count.

REMEMBER Patients should be weighed at every single

visit! If weight loss is occurring, it could represent a serious problem, so it should not be ignored! Check thoroughly for TB before blaming the weight loss on HIV wasting syndrome! Clinical management
eigh the patient at every visit. Also ask about weight loss at the first W consultation. Estimate the percentage of weight lost; loss of > 10% of previous body weight is considered serious and the cause must be identified ASAP. Record a childs height regularly. Complete a thorough clinical examination to identify any: Oral problems affecting food intake: aphthous ulcers or dental problems causing pain; oral and/or oesophageal thrush causing difficulty swallowing. Chronic diarrhoea and/or vomiting. Loss of appetite induced by an opportunistic infection (TB is by far the most common cause). High lactate (an uncommon, but serious side effect of ARVs) can initially present as weight loss. If you notice weight loss in a person taking ARVs (especially D4T), then do not ignore it. It is serious and must be investigated.

29

Improving nutrition alone will not necessarily improve the weight of patients in the final stage of HIV infection (Stage 4 = AIDS). ny underlying infection must be identified and treated A (especially TB). If no infections are identified and HIV itself is the underlying cause of the weight loss (HIV wasting syndrome) then it requires treatment with nutrition plus ARVs in order to prevent death!
Symptom Management

Try to make sure that the patient has access to quality food. Refer to a nutritionist for fortified food supplements if available. Also refer to a social worker if the patient cannot afford food.

Energy-rich and protein-rich food should be given together with adequate micronutrients (vitamins and minerals). If possible, physical exercise helps to increase appetite. Clients who are losing weight should be monitored until the cause is found or the weight loss reverses.

REMEMBER
Tuberculosis (TB) is the most common cause of death in our patients. TB is more difficult to diagnose in HIV-positive people and may occur outside the lungs (EPTB). Weight loss is one of several non-specific signs that an HIV-positive person may suffer as a result of active TB. Arrange for further investigations (Chest X-ray, CRP, TB culture, etc) if you suspect TB, even if the sputum smears are negative!

30

Symptom Management

Algorithm 1: Investigation of Weight Loss

> 5% body weight or > 4 kg in total or on 3 consecutive visits Not on ART Always screen for TB (symptoms & sputum; see algorithms 7 & 8, p. 86 & 98)

On ART

If on ART for > 4 months (especially d4T), check lactate level If lactate > 2, see algorithm 16 (p. 177)

Check for oral thrush and painful swallowing (see algorithm 4, p. 60)

If abdominal pain: check ALT and lipase to exclude hepatitis and pancreatitis (see appendix 12, p. 223224).

Check for diarrhoea (see algorithm 5, p. 68)

Check for abdominal pain Check last viral load result. Failing ART can lead to weight loss. If high viral load see algorithm 14 (p. 169) Check glucose for diabetes (algorithm 6, p. 74)

Check for lipodystrophy (changes in fat distribution), especially if on d4T or ddI. See Appendix 12. (p. 223). Consider TB and malignancy: do PAP smear, FBC, chest X-ray and check for lymph nodes

Check for other adverse events of ARVs: nausea and vomiting; chronic diarrhoea, diabetes. See appendix 12 (p. 223) Check for depression (see p. 122)

31

Headache
There are many possible causes of headache, most of which are not life-threatening. However, one must not miss those relatively few patients who are presenting with a life-threatening cause for the headache! An HIV-infected person having headache and one or more of the warning symptoms/signs in Algorithm 2 on page 33 might have meningitis.
Symptom Management

Causes
Common causes are: igraine M Sinusitis Muscle strain (neck) Eye strain Tension headache or stress Any infection causing high temperature Hypertension Dehydration Dental infections

Clinical management
When to refer You should refer the patient to the doctor if one of the following applies: The patients CD4 count is < 100 cells/L. The headache is very severe. The headache is associated with fever, neurological symptoms, change in behaviour, confusion, neck stiffness, vomiting, or difficulty with vision. N.B. The lower the CD4 count, the more you should suspect meningitis! If in doubt, REFER for lumbar puncture (LP) irrespective of the duration or severity of the headache. Examination A complete and careful clinical examination is required to look for: igns of meningitis: neck stiffness, Brudzinskis sign, Kernigs sign S Hypertension (high blood pressure) Signs of disorientation or confusion

32

Symptom Management

Localising signs (such as one-sided weakness or hemiplegia) Signs of raised intracranial pressure: papilloedema on retinal examination Signs of generalized infection: fever (temperature 38 C), hepatomegaly, splenomegaly, rash. Visual changes (e.g. double vision, photophobia) Associated seizure

REFER
Signs and symptoms including one or more of the above may represent meningitis. Treat with: Ceftriaxone 2 g IM/IV (If none available, give penicillin G 5MU IV stat). Arrange same day referral to hospital.

Lumbar puncture When indicated, a lumbar puncture must be performed urgently to rule out possible serious causes (listed in order of likelihood): Bacterial meningitis TB meningitis (TBM) Cryptococcal meningitis (CCM) Viral meningitis (e.g. HSV) Neurosyphilis

CSF investigations should include the following: cell count, bacterial culture, CLAT/ CRAG, VDRL, AFB, and TB culture.

33

Algorithm 2: Investigation of a Headache in an HIV patient

Headache in an HIV patient

Symptom Management

If any of the following are present:

Fever

CD4 count < 100 cells/L Confusion

Vomiting

Headache is severe Neck stiffness

New-onset seizures

Change in vision

No response to painkillers

Focal signs (such as one-sided weakness)

Refer for Lumbar Puncture!!!

34

Symptom Management

Confusion
Confusion is common in the late stages of HIV infection.

Causes
Possible causes are: Any severe infection eningitis M HIV-related encephalopathy Cytomegalovirus infection of the brain (perform retinal examination through dilated pupils for CMV retinitis) Progressive multifocal leukoencephalopathy (PML)

Diagnosis
All patients presenting with new-onset confusion (and/or new onset seizures) need to be referred for lumbar puncture (LP) in order to exclude meningitis (cryptococcal or other types) and/or other treatable severe infections (syphilis, toxoplasmosis, etc).

Management
If a lumbar puncture does not reveal any reversible abnormality and any acute OI is being treated, all HIV-infected patients with disorientation and confusion of unknown cause should be started on ARVs if feasible (if family or other supports are available). The patients condition often improves after ARVs are started. Otherwise treatment is palliative. The following nursing care is vital: revention of bedsores (see page 56) P Assistance with personal hygiene Support for the patient and the family (home based care) Appropriate pain management if needed (see page 183)

Admission to a hospice is invaluable for many of these patients, both to provide nursing care, and to initiate ARVs in a supervised setting. Once the patient improves on ARVs, the patient and family can be counselled about the need for adherence, and then discharged home with good support (home-based care).

35

Lymphadenopathy
Lymphadenopathy (enlarged lymph nodes) is often a result of infection but can also be caused by cancer (e.g. lymphoma or Kaposi sarcoma). The lymphadenopathy can be generalised or localised. Do not confuse enlarged lymph nodes with swollen parotid glands (in the cheeks) or other salivary glands (Diffuse Infiltrative Lymphocytosis Syndrome or DILS).
Symptom Management

Causes of lymphadenopathy
Causes of generalized lymphadenopathy HIV itself (but often < 2 cm in size) Secondary Syphilis

Causes of localised lymphadenopathy: Tuberculosis Bacterial infection STIs (groin) Kaposi Sarcoma (KS) Lymphoma

REMEMBER

Think of TB when a person presents with any enlarged lymph node that is chronic!

Clinical presentation
wollen lymph nodes S Sometimes tender Located in neck, axillae, or groin

Clinical examination
ody temperature B Assess for weight loss Measure and note size of lymph nodes (fine needle biopsy indicated if > 2 cm, see Appendix 29) Check all other lymph node areas (neck, axillae, groin) Check for liver or spleen enlargement

Management
orrect management depends on the specific diagnosis, so it is important to C make an accurate diagnosis.

36

Symptom Management

A trial of antibiotic therapy is reasonable for localised enlarged lymph nodes, especially while waiting for needle biopsy results: flucloxacillin 250-500 mg four times daily x 5 days (depending on weight of adult).

If the node is > 2 cm in adults, needle aspiration should be performed by a trained clinician as follows: If the node is fluctuant, aspiration is easy and can be performed by the nurse or doctor; liquid aspirate should be sent in a sputum jar for TB testing (AFB +/- culture). If the node is not fluctuant, a fine needle aspiration biopsy (FNAB) should be performed by a trained clinician and the material sent on slides for AFB examination and cytology to rule out other possible causes (lymphoma, KS, etc). See Appendix 29 for detailed information on how to perform a FNAB

Needle biopsy material should be sent for: TB smear (AFB) Cytology (to identify any lymphoma)

37

Notes
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Symptom Management

38

Symptom Management

Notes
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Skin Conditions

Wayne Conradie

40

Skin Conditions

Algorithm 3: Diagnosis of a Rash in an HIV-positive patient

Rash in HIV Patient

Painless bumps (+/- itching)

Painful bumps

Flat lesions (+/- itching)

If dimpled, think of molluscum If pustules, treat for bacterial folliculitis If in genital area, think of warts due to HPV If dry skin only (xerosis), treat with moisturizer

If very itchy, treat for scabies

If blisters (becoming crusted) on lips or genitals, think of HSV

If circular or involves skin creases, treat as tinea

If no improvement, treat as P.P.E. If blisters (becoming If bumps are dark, slowly enlarging and feel deep, think of KS (and refer for ARVs if confirmed!) crusted) in localized area on one side of body, treat for shingles If palms or soles are affected, think of syphilis (check RPR/VDRL and treat accordingly)

Refer to hospital on the same day and stop all drugs, if the patient recently started cotrimoxazole, TB drugs, or ARVs, and presents with skin rash plus one or more of the following: Temperature 38 C Systemic symptoms (generally unwell, vomiting, abdominal pain, headache) Rash affecting lips, mouth, eyes, genital and/or anal area. Blistering or raw areas Diffuse purple discoloration of the skin affecting the whole body

41

Xerosis (Ichthyosis)
Definition
Xerosis means dryness of the skin.

Clinical presentation
Xerosis is common (> 20%) in HIV infection and is characterised by: Dry skin with slight to pronounced scaling Itching (sometimes severe) Watch for bacterial super-infection (which causes a yellow crust +/- weeping in addition to the xerosis)
Skin Conditions

Treatment
Topical: Emulsifying ointment to moisturize (in adequate amounts = at least 500 g per month) Use aqueous cream as soap If very itchy, add betamethasone 0.1% ointment (Lenovate) twice daily for 7 days Limit the use of steroid to short-term as they may cause skin atrophy or a paradoxical reaction. Try to avoid using steroid preparations on the face. Systemic: romethazine 25 mg or Chlorpheniramine 4 mg at night as required will reduce P itching at night, but prescribe this only if the itching is severe.

Children
imit the use of promethazine to 35 days max, if itching is severe L

Promethazine dose Age < 2 years 25 years 510 years Dose Not recommended 515 mg/day 1025 mg/day

42

Skin Conditions

Papular pruriginous eruption (PPE)

Follicular papules and nodules disseminated over the body

Clinical presentation
Painless but itchy Often with infected crusts Can temporarily worsen after starting ARVs.

Management
Always treat for Scabies first (see below); if no response, treat for PPE. Topical: Betamethasone 0.1% ointment twice daily for 10 days, alternated with emollients (emulsifying ointment, Vaseline, or HEB simplex) twice daily for 10 days. Zinc oxide compound, applied twice daily for 2 weeks

Systemic: romethazine 25 mg or chlorpheniramine 4 mg at night as required for severe P itching. If bacterial infection (presence of pus or yellow crusts): Apply Savlon or povidone-iodine solution topically twice daily If severe, add flucloxacillin 250-500 mg four times daily for 5 days (actual dose depends on body weight and severity of super-infection). PPE is a stage 2 diagnosis. Client needs cotrimoxazole prophylaxis.

Children
Topical: ydrocortisone ointment 0.5-1% twice daily for 7 days followed by emollients H twice daily for 7 days. Use steroids starting with low strength usually hydrocortisone 0.5-1%, then increase strength until the problem is controlled (note that betamethasone 0.1% is stronger than hydrocortisone 1%). An alternative is Modified Adamsons (tar and steroid). The tar component has anti-inflammatory and insect repellent properties. Apply to all areas affected.

Systemic f severe itching: promethazine, 0.1mg/kg PO 6 hourly (limit use to a few days I and use only in children > 2 years). See Table on page 41.

43

Scabies
Scabies is a frequent contagious skin infection caused by mites. It is transmitted by close contact (including handshakes and sexual contact).

Clinical presentation
xtremely itchy E Papular lesions with linear burrows sometimes seen Predominantly on hands (in finger web spaces), wrists, armpits, abdomen and genitals; in infants, also on palms and soles Common in children Often a history of itching contact Sometimes a severe form of scabies is seen: Norwegian (crusted) Scabies: presents as thick, greyish crusts, often on elbows or wrists. Such cases are highly contagious with thousands of mites, so isolate this person! Management his should include the patient and all household contacts (whether T symptomatic or not). Topical: 5% benzyl benzoate lotion applied to the entire body except the face, eyes, 2 and mucous membranes. Wash off after 24 hours and repeat 72 hours later. Wash clothes and bed sheets on the same day (very important to prevent reinfection) Chlorpheniramine 4 mg or promethazine 25 mg to be taken as needed at night for itch Systemic: f scabies is severe or resistant to Benzyl Benzoate, add: Ivermectin tablets 200 I micrograms/kg once (STAT dose on empty stomach). This should be combined with topical therapy (see above).
Skin Conditions

Children
scabiol (topical benzoate benzyl 25%) - apply to whole body from neck down A (including between fingers, along the nail edges, palms/sole and the genitalia). Leave on for 12-24 hours, and then wash off. Repeat the following day, and again in 1 week. (Dilute 1:1- with an equal amount of water - for children between 6 months and 5 years). For infants less than six months age use 5% sulphur ointment as above.

44

Skin Conditions

Dont forget to treat all household members at the same time and wash bed sheets and clothes. In severe cases, treat with ivermectin in children over 15 kg (15-25 kg: 1 tab of 3 mg; 25-45 kg: 2 tabs of 3 mg).

Tinea pedis (Athletes foot)

Fungal infection caused by Trichophyton rubrum.

Clinical presentation
eeling, cracking and scaling skin between the toes (giving a cooked P appearance) Occasional redness and blisters on the soles and sides of the feet. Associated with burning and/or itching.

Management
eep the toes and web spaces dry. Advise use of sandals if possible. Change K socks as often as possible (and/or avoid sports shoes). Encourage open shoes/ sandals. Talcum powder can be used to help the skin dry up and can also be sprinkled into the socks to absorb sweat. Miconazole 2% or clotrimazole 1% cream applied twice daily for 2 weeks or until resolved. If fingernails involved, consider us of griseofulvin. Give advice about contraception if drug-drug interaction with griseofulrin. Refer if no response to treatment. Fungal nail infection is a stage 2 diagnosis, so need to give cotrimoxazole prophylaxis

Tinea corporis (also known as Ringworm) or Tinea capitis

Fungal infection of the skin caused by different types of fungus. Note that this infection has nothing to do with worms!

Clinical presentation
ircular lesion with a raised, red, active edge (sometimes looks worm-like on the C edges!) with scaling and papules on the inside.

45

Management
Topical: iconazole 1%, clotrimazole 2%, or Whitfields ointment applied twice daily for M several weeks, until lesions are cleared. Advise client not to share towels/clothes (very infectious). For tinea capitis (scalp lesions): Selenium sulphide (Selsun) shampoo can be used. Leave on for 30 minutes daily for a week; then use 2-3 times a week until tinea is cleared. Systemic: n case of topical treatment failure, extensive scalp lesions, and/or disseminated I infection, oral therapy may be required. Fluconazole 200 mg daily for 1 month (adults) or griseofulvin 500 mg to 1 g per day in one or two doses for 4 weeks for skin infections, 8 weeks for scalp, and 3 to 6 months for nail infections. Griseofulvin needs to be taken after food or milk. If added bacterial infection: Savlon may be used for local cleaning plus Flucloxacillin 250-500 mg orally 4 times a day for 5 days, or If penicillin allergic, erythromycin 500 mg 4 times a day for 5 days.
Skin Conditions

Once the infection has cleared, proceed to antifungal topical cream.

Children
or tinea corporis: Whitfields ointment is effective in non extensive lesions. F Use oral griseofulvin (20 mg/kg/day in 2 doses) for at least 6 weeks if nonresponsive or extensive. Griseofulvin should be crushed and taken with food or milk. Other alternatives are imidazole cream or fluconazole orally depending on severity. For tinea capitis: Griseofulvin 20 mg/kg/day in two doses for 6 weeks; add Betadine or Savlon shampoo for antibacterial and additive antifungal effects. If scaly, use salicylic acid 2% or aqueous cream over night.

46

Skin Conditions

Seborrheic dermatitis
Chronic skin condition occurring most commonly on the scalp and face in clearly defined areas (seborrheic areas). Seborrheic dermatitis is often mistaken for fungal infections of the skin (tinea).

Clinical presentation
On and off red patches, often itchy or burning Sometimes scaling with a yellowish appearance Involving seborrheic areas (naso-labial folds, sternum, head, outer ear, inguinal area and armpits).

Management:
ild steroid cream (such as Hydrocortisone cream 1%) twice daily on the skin M Selenium sulphide (Selsun) shampoo (or tar shampoo if available) 2-3 times weekly if the scalp is involved. Application is easier if hair is cut short. If bacterial super-infection, treat with flucloxacillin 250 mg 4 times a day for 5 days. If penicillin allergic give erythromycin 500 mg 4 times a day for 5 days. If poor response to treatment, refer to doctor.

Children
queous cream as soap A Face and flexures: 1% hydrocortisone cream once or twice daily If more severe use Lenovate (betamethasone valerate) 1:10 in aqueous cream

Nappy Rash
Infant rash caused by irritation from persistent moisture and irregular cleaning and drying of napkin area.

Management
nsure nappy is changed frequently E If very mild, a barrier cream with each nappy change should be sufficient e.g. zinc ointment or castor oil If more inflamed, apply 1% hydrocortisone cream BD under the barrier cream If signs of infection with Candida, use clotrimazole cream. Suspect Candida if skin folds are involved or there is no improvement with above treatment after 3 days.

47

Herpes Simplex (HSV)

Very common infection caused by Herpes simplex virus, type 1 or 2 (HSV-1 or HSV2). Genital HSV infection is one of the main triggers of HIV transmission, so treating genital HSV (in addition to condom use) will help to prevent new HIV infections in the general population!

Clinical presentation
ips: HSV of the lip is sometimes called a cold sore. It starts as a group of tiny L blisters involving the edge of the lip (or occasionally the area under one nostril) which can form small ulcers, then heal by forming crusts. Mouth ulcers can be caused by HSV (see algorithm 4, page 60) Genital area: Genital HSV occurs in women more than men; often multiple deep ulcers occur in the genital area or around the anus. Genital HSV is very painful, and sometimes causes urinary retention!
Skin Conditions

Management
ips: usually do not require treatment unless severe, as they resolve on their L own. Do not manipulate. Keep the lesions dry! Gentian violet may be applied twice daily. Genital herpes: Acyclovir 400 mg three times daily for 10 days. In very severe cases, acyclovir 800 mg three times daily can be given. If chronic ulcers: continue treatment until ulcers have healed. Chronic HSV infection (7 one months duration) = clinical stage 4, so fast-track for ART. Do not forget painkillers! Pain control: Ibuprofen 400 mg, three times daily or paracetamol + codeine, 500 mg three times daily. +/- carbamazepine, oral, 100 mg twice daily, increased every 12 hours until pain is relieved (maximum 1.2 g/day). If the patient is on ARVs, it is preferable to use amitriptyline, 25 mg at night instead of carbamazepine. Admit to hospital if problems urinating.

Children
ften seen on tongue, lips, all mucosal surfaces, around mouth and nose O May be recurrent or chronic

48

Skin Conditions

May have secondary bacterial infection Treatment with oral acyclovir Under 2 years: 200 mg 8 hourly for 5 days 2 years and over: 400 mg 8 hourly for 5 days A repeat course may be required

Pain relief (see page 186)

Molluscum contagiosum
A skin rash caused by a poxvirus; especially common in children.

Clinical presentation
kin-coloured papular lesions, umbilicated (dimpled) in the centre S Often on the face, also common on trunk and genitalia, but may occur anywhere on the body; single or in clusters. May be extensive in HIV.

Management
eassure (usually resolves quickly with ARVs but may get worse first before R getting better). The lesions can be squeezed out or removed with a large sterile needle or scalpel, followed by disinfection with Savlon or povidone-iodine or paint with tincture of iodine. This is essential as the white material contains poxvirus and new lesions will appear if not properly disinfected. If available, cryotherapy (freezing) works very well. Refer if no improvement on ARVs.

Children
o treatment required unless troublesome. Likely to disappear as immune N status improves. Discuss with doctor about possible treatment with Cantharidin paint (Wart paint), liquid nitrogen, pricking with injection needle, or curettage.

49

Warts
A skin condition caused by a virus (Human Papilloma Virus). Different sub-types of the virus cause genital and non-genital warts.

Clinical presentation
Multiple papules; may be raised or flat Commonly on hands, face, feet and genitals. See pages 134135 for the management of genital warts For non-genital warts, reassure that they generally disappear on their own or with improved immune status. For children with extensive flat warts, this may however take time, even after ARVs have been started. Various methods of treatment may be used for individual lesions (salicylic paint, cryotherapy, podophyllin or chloroacetic acid). Be careful not to burn surrounding health skin, as warts may then appear on the damaged skin.
Skin Conditions

Management

Bacterial Folliculitis
Folliculitis is the infection of one or many hair follicles. It is caused by bacteria (Staphylococcus species).

Clinical presentation
ainful yellow pustules (blisters filled with pus) with a red halo. P Note that fungal infections, especially of the scalp and beard, may be mistaken for bacterial folliculitis.

Management
Topical avlon fluid or povidone-iodine (mixed 1:10 with water) applied twice daily. S

Systemic: idespread or severe: flucloxacillin 250-500 mg four times daily x 7 days. W Flucloxacillin has to be taken at least 30 minutes before food. If allergic to penicillin use erythromycin 500 mg 4 times a day for 7 days.

Children
lucloxacillin 12-25 mg/kg/dose (max 500 mg/dose) 4 times daily for 7 days: F < 5 kg: 62.5 mg 510 kg: 125 mg 1020 kg: 250 mg

50

Skin Conditions

Impetigo
Crusting superficial sores usually seen around mouth or nose. Deeper lesions can be seen on the legs. Caused by bacteria: Staphylococcus aureus or Streptococcus pyogenes.

Children
ash off the crust W If very localized, topical agents are usually enough e.g. Betadine or Flamazine If more extensive, then oral erythromycin 10 mg/kg/dose four times daily, or Oral flucloxacillin four times daily for 7 days (dosage as for folliculitis) Keep fingernails clean and short

Herpes Zoster (Shingles)

Herpes zoster is caused by a reactivation of Varicella-Zoster virus infection. This is the same virus that causes chickenpox during childhood. After the chickenpox heals, the virus lies dormant in our bodies, but reactivates (as Shingles) if our immune system becomes weak (due to stress, old age, or HIV).

Clinical presentation
Herpes zoster is characterised by: n eruption of blisters on one side of the body, usually involving one A dermatome (one area of skin supplied by a spinal nerve). The blisters crust over after 1-2 weeks (with or without treatment) and then heal, but often leave a scar. The blistering is usually accompanied by burning pain that often precedes the skin lesions and may continue even after healing of the rash has taken place. Pain after healing of the rash is called post-herpetic neuralgia.

Management of shingles
Acute topical treatment eep area warm (reduces likelihood of post-herpetic neuralgia). K Topical treatment with povidone iodine cream or silver sulphadiazine cream.

Acute systemic treatment f the rash has been present for > 72 hours before the patient comes to the clinic, I then Acyclovir is not necessary and painkillers are the only treatment required. The rash will slowly heal on its own.

51

Consider Acyclovir 800 mg five times daily for 7 days if the rash has been present for <72 hours. Pain control: Amitriptyline 25mg nocte plus Ibuprofen 200 mg 1-2 tablets 3 times daily, as required and/or paracetamol 500mg + codeine phosphate 8 mg, 1-2 tablets four times daily as required (maximum 8 tablets daily).

A stage 2 diagnosis. Client needs cotrimoxazole prophylaxis.

Treatment for chronic pain (after healing of rash) If Chronic pain (post-herpetic neuralgia) develops: mitriptyline 25 mg daily at night, to be increased as required up to 100 mg A daily
Skin Conditions

REFER
If shingles involves the eye: give acyclovir tablets as above, plus chloramphenicol eye ointment as a lubricant. Refer to an eye doctor on the same day! If shingles occurs in the ear canal, it may lead to deafness (Ramsey Hunt Syndrome). Refer to an ENT surgeon as soon as possible!

Children
ommon in all HIV infected children regardless of CD4% or count. C Can also present as Immune Reconstitution Inflammatory Syndrome (IRIS) Oral acyclovir for 7 days if within 72 hours of rash or eye involvement: Under 2 years: 200 mg 4 times daily 2-5 years: 400 mg 4 times daily Over 6 years: 800 mg 4 times daily

Pain control: Ibuprofen, orally 5-10 mg/kg/dose every 6-8 hours, as required (Max 40 mg/kg/day): 3-6 months (weight over 5 kg) 50 mg 3-4 times daily; 1-3 years 100 mg 3 times daily; 4-6 years 150 mg 3 times daily; 7-9 years 200 mg 3 times daily; 10-12 years 300 mg 3 times daily. Paracetamol 500 mg + codeine 8 mg: 6-12 years, -1 tablet 3-4 times daily (maximum 4 tablets daily). For smaller children, see Tables 18 and 19 page 186.

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Skin Conditions

Varicella (chickenpox)
Clinical presentation
Prodromal symptoms (fever, headache, feeling unwell) for 2 days prior to the onset of rash Presents with vesicles, which start as papules and eventually become crusted, distributed over face, trunk and limbs. Vesicles appear in crops over several days. Mucosal surfaces may also be involved. The child with immune suppression may have large and extensive vesicles and is more likely to have complications.

Management of chickenpox
Isolate the child if possible, since contagious from day 2 before the rash appears until lesions have completely crusted over Treat with acyclovir 80 mg/kg per day orally given 4 times a day for 7-14 days (see dose given for Herpes Zoster) Provide pain relief If secondary bacterial infection develops, add amoxicillin 10-25 mg/kg/dose three times a day and flucloxacillin 12-25 mg/kg/dose four times a day. Prevention and PEP: Varicella immunoglobulin (VZIG) is recommended for children who have been exposed to chickenpox (must be given ASAP and within 96 hours for maximum efficiency). The varicella vaccine can be used both as prevention and post-exposure prophylaxis if given within 3 days of exposure. Refer to hospital if: Appropriate medication is not available Disseminated infection is suspected (pneumonia, jaundice, abnormal neurological findings) The child is unable to ingest fluids or the child is dehydrated

Kaposi sarcoma (KS)

KS is caused by Human Herpes Virus, type 8 (HHV-8). Kaposi sarcoma is a cancer originating from the inner lining of blood vessels. It affects mainly the skin and mucous membranes, but also any organs inside the body (for example, the lungs). KS lesions signify that a person is in stage 4, regardless of their CD4 count.

53

Clinical presentation
ark, purple papules on the skin or palate, starting as single lesions which D progressively grow, multiply, and disseminate to other parts of the body. Lesions range from small bumps to big tumours. The nose, palate, legs, and genitals are most often affected. KS is sometimes associated with swelling of the affected leg (lymphoedema).

antiretrovirals (ARVs) as soon as possible regardless of their CD4 count! Refer the same week for ARVs, as well as to a specialist for chemotherapy and/or radiation.

REMEMBER Patients with KS must be enrolled for

Skin Conditions

Management
ssess for signs suggesting inner organ involvement (pleural effusion, blood in A stools, chronic cough, and/or ascites). Every patient with KS should have a chest x-ray and a thorough examination of the mouth. Initiate ARVS as soon as possible. Refer to doctor the same week to assess need for chemo- or radiotherapy. Ideally, patients with large lesions should be referred to a specialist for chemotherapy and stabilisation of KS before starting ARVS. This helps to limit KS immune reconstitution inflammatory syndrome (IRIS). Patients with CD4 counts below 50 should be started on ARVs as soon as possible, regardless of how aggressive the KS lesions are. Always make a note of KS lesion(s) on each visit to assess growth or regression; you may need to measure lesion(s) for an accurate assessment.

Dont forget that KS can occur in children of any age (although not as common as in adults).

REMEMBER

Always examine the child completely undressed to look carefully at the entire skin. Always examine the mouth.

54

Skin Conditions

Drug rash
All drugs have the potential to cause side effects. One such possible side effect is a skin rash, sometimes referred to as a drug eruption or drug rash. Common causes of drug rashes include cotrimoxazole, TB drugs, and some ARVs (especially nevirapine; but also efavirenz). The rash caused by nevirapine usually presents within the first three weeks of treatment (often just after increasing the dose to 200 mg twice daily). Taking a good history is one of the main ways of making a diagnosis of drug rash. Whenever assessing a person with a new rash, always ask about any new medications.

Common manifestations
oin-like lesions, well demarcated, often hyperpigmented (dark) and painless. C Reddish, flat or raised lesions, usually widespread, often itchy or painful. Less commonly, a severe rash can develop (called Stevens-Johnson syndrome) and involve the mouth, eyes and/or genitalia (always look). If this occurs the patient needs to be referred immediately to a doctor or hospital. The offending drug must be stopped immediately.

Management
Severe rashes sually involves stopping the drug in question. See specific sections regarding U management of drug eruptions due to different drugs.

REFER
Refer to hospital and stop all drugs if the patient recently started cotrimoxazole, TB drugs, or ARVs, and presents with skin rash plus one or more of the following:
Temperature 38 C Systemic symptoms (generally unwell, vomiting, abdominal pain, headache) Rash affecting lips, mouth, eyes, genital and/or anal area. Blistering or raw areas Discoloration of the skin affecting the whole body

55

Non-severe rashes o not stop drugs. D Send blood for ALT. Review the following day with result. (See Appendix 17 for interpretation.) Advise client to return urgently if any serious symptoms/signs develop. Provide symptomatic relief with emulsifying ointment. There is no role for topical steroids in drug rash.

Psoriasis (if severe should be managed by dermatologist then referred down to clinic)
A skin (and joint) condition that may present shortly after infection with HIV. Psoriasis is more common in HIV-infected people. There may be a genetic predisposition.

Skin Conditions

Clinical presentation
caling, reddish plaques involving scalp, knees, elbows, abdomen, palms and S soles. Rash may be atypical in HIV-infected people (groin, armpits, etc.) Involvement of nails (pits) and/or joints (psoriatic arthritis), especially the foot and ankle.

Management
Always refer to dermatologist Counsel regarding chronic course of psoriasis and encourage sun exposure as tolerated. Adults: salicylic acid 2-10% in white soft paraffin, topical, applied 3 times daily until scale is removed. Then: betamethasone 0.1% ointment or modified Adamsons ointment twice daily to plaques.

Children:
Hydrocortisone 1%, topical, applied 1-2 times daily In severe cases: prednisone, orally, 1-2 mg/kg as a single dose for 7 days

56

Skin Conditions

Bedsores (or Pressure Sores)

Bedsores are caused by pressure on certain body parts as a result of prolonged periods in bed without changes in position. This leads to death of skin and soft tissue.

Clinical presentation
Bedsores are characterised by: lcers of varying depth, located on pressure points of bones U They are often secondarily infected and discharging pus

Management
Very difficult to manage! each the caretaker to reduce the pressure on affected areas as much as T possible (change position every 3-4 hours, and use properly-arranged pillows)! Wash with saline solution and then dry. Apply Zinc oxide compound around the wound, and Savlon on the wound. If secondarily infected: Metronidazole 400 mg + Amoxicillin 500 mg three times daily for 10 days. If Pseudomonas bacterial infection is suspected (bedsore has a greenish appearance and sweet smell), give ciprofloxacin 500 mg twice daily +/gentamycin IM injection (and consult doctor!).

Children
For secondarily infected bedsores give: Metronidazole 30 mg/kg/day in three or four daily doses for 10 days: 1-3 years 100-200 mg 3 times daily; 3-7 years 200 mg 4 times daily; 7-10 years 200-400 mg 3 times daily; above 12 years same as for adults, and Amoxicillin three times daily for 10 days: < 20 kg 15-25 mg/kg/dose; > 25 kg same dose as for adults. If Pseudomonas infection is suspected, give ciprofloxacin 15 mg/kg/dose twice daily +/- gentamycin 7.5 mg/kg IM injection (and consult doctor).

57

Notes
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Skin Conditions
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58

Skin Conditions

Notes
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Mouth Lesions

Wayne Conradie

60

Mouth Lesions

Algorithm 4: Clinical Management of Difficulty Swallowing

Difficulty swallowing (with or without pain)

Look in mouth

No ulcer or thrush

Oral thrush

Ulcer seen

CD4 count > 200

CD4 count unknown or low (< 200)

Consider reflux as cause

Suspect oesophageal thrush and treat with fluconazole (person will usually be losing weight)

If no improvement

Treat with acyclovir (as HSV is a possible cause, especially if there is a lot of pain)

Improved

If no improvement

Note: If purple KS lesions are seen Prepare to start ARVs! Refer to doctor for assessment

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Oral health
Basic oral health is important to prevent infections of the oral cavity, as these occur with increased frequency in HIV-positive people. This includes: egular brushing and flossing of teeth. R Do not share a toothbrush! Advise a visit to the dentist if gum disease or dental cavities are present.

Oral candidiasis (oral thrush)

Oral candidiasis is caused by yeast called Candida. It occurs in newborns, the elderly and those who have very weak immune systems. Remember: the very young, the very old, and the very sick. It is a serious symptom in HIV-infected patients indicating advanced immunodeficiency! It places an adult and a child in stage 3 of HIV infection (see Appendices 1 and 2).
Mouth Lesions

Clinical presentation
Oral candidiasis has two presentations: Pseudomembranous presentation (thrush): white patches (which can be removed with a tongue depressor) surrounded by a reddish border; these involve mostly the inner mucosa of the mouth, the pharynx and the inner lips. Thrush may present as a reddish discoloration and burning of the hard palate (atrophic thrush). This may be difficult to diagnose. Patients often complain of having no taste.

Ask about painful swallowing and difficulty swallowing, which suggests coexisting oesophageal candidiasis (see page 64).

Management
ystatin oral suspension 2-5 ml to be swished around the mouth for as long as N possible five times daily. If it still persists then use: amphotericin B lozenges or nystatin tablets (vaginal tablets, 100 000 IU) 1 sucked 4 times a day for 5 days or 0.5% gentian violet aqueous solution painted in mouth 3 times a day. Refer for fluconazole 50-100 mg once daily for 10 days if : The thrush is severe or recurrent No response to amphotericin B lozenges after 5 days

62

Mouth Lesions

Children:
In infants, it is sometimes accompanied by a candidal napkin rash. If persistent despite adequate treatment, it is strongly suggestive of HIV infection. Nystatin drops 1 ml 5 times daily for 7 days +/- 30 minutes after feed for 7days. Continue for 48 hours after cure. If no response / poor response add miconazole (Daktarin) gel 4-6 hourly for 7-14 days. Gentian violet can also be use as an alternative (child should not swallow fluid, needs to be applied on the tongue and mouth). For pain use benzydamine (Andolex) or choline salicylate/cetalkonium chloride (Teejel or Bonjela) mouthwash, and/or paracetamol 20mg/kg/dose 3 times daily (see Table 18 page 186). Treat refractory candidiasis with fluconazole 3 mg/kg/day for up to 21 days.

REMEMBER

All patients with oral thrush should be assessed for ARVs!

Angular stomatitis (cheilitis)

Angular stomatitis is also caused by Candida.

Clinical presentation
nvolvement of the corners of the mouth, presenting as a fissure (or crack) I Can be painful

Management
eep dry and avoid mechanical irritation. K Nystatin/clotrimazole cream or oral gel twice daily for 10 days is very effective.

63

Aphthous ulcers (Canker sores)

Clinical presentation
ne or more ulcers on the mucosa of the mouth, the inner lips, and sometimes O the tongue. Very persistent and very painful (10 days). Cannot be differentiated from herpetic ulcers (caused by HSV). Do not forget syphilis as a cause (but these are less painful).

Management
void acidic foods. A Prescribe painkillers (see Pain Chapter page 183) Give acyclovir 400 mg three times daily for 10 days in case of HSV.
Mouth Lesions

Oral hairy leukoplakia

Oral hairy leukoplakia is caused by Epstein-Barr Virus. It is specific to HIV infection, and indicates immunosupression. It places a client in stage 3 of HIV infection. Occurs mostly in adults. However, it is worthwhile to look for it in children because if found, the child is stage 3 and therefore eligible for ARVs.

Clinical presentation
ery typical appearance: white raised vertical lines (Adidas stripes) on the V edges of the tongue.

Management
o treatment necessary. Often disappears after ARVs are initiated. N

64

Mouth Lesions

Oesophageal candidiasis (oesophageal thrush)

Since the oesophagus (the muscular tube carrying food from the mouth to the stomach) cannot be seen, a diagnosis of oesophageal thrush is not easy to make. Usually, the nurse or doctor has to rely on a good history to make such a diagnosis.

Clinical presentation
esophageal thrush must be suspected when someone with a low CD4 count O complains of difficulty swallowing, or pain on swallowing, especially if oral candidiasis is present. In immunocompromised patients, it is often associated with a critical decrease in food intake, and consequent weight loss. Possible causes of painful and difficult swallowing include: Gastro-oesophageal reflux disease (GERD) Infection of the oesophagus with cytomegalovirus (CMV) An oesophageal aphtous ulcer not related to HSV Kaposi sarcoma (KS)

Management
atient must be enrolled for ARVs as soon as possible! P Fluconazole 100-400 mg daily for 10-14 days, then check the response to treatment after 7 days. If there is a good response, then oesophageal candidiasis is the likely diagnosis and the patient is then considered to be in stage 4. Continue the fluconazole for 10 days to 2 weeks. If fluconazole is not effective after one week, consider HSV as the possible cause of the painful swallowing and prescribe acyclovir 400 mg three times daily for 10 days. If acyclovir is not effective, then refer to the doctor for further assessment.

REMEMBER
If someone with a high CD4 count is complaining of retrosternal pain but is not sick (and not losing weight), that person does not have oesophageal thrush (and is therefore not in stage 4!). The diagnosis in this case is more likely to be reflux requiring antacids (not fluconazole).

65

Children
ifficult to diagnose in infants. Suspect if infant has oral candidiasis associated D with crying and/or refusal to feed. Treat with fluconazole 3 mg/kg/day for 21 days. If there is no improvement after 7 days, and HSV is suspected, prescribe acyclovir 20 mg/kg/dose three times daily for 10 days. Child needs admission to hospital if he/she does not tolerate food and has signs of dehydration.

Mouth Lesions

66

Mouth Lesions

Notes
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Gastro-intestinal Conditions

Sophia Ioannou

68

Gastro-intestinal Conditions

Algorithm 5: Management of Diarrhoea

Diarrhoea in HIV patients
> 2 weeks < 2 weeks Diarrhoea is self-limiting

Rehydration measures, plus nutritional advice

Acute Diarrhoea

Chronic Diarrhoea Frequent stools

Acute Diarrhoea treatment already received Acute Diarrhoea treatment not yet received

with fever and/ or cramps

If blood is present

O.R.S. + cotrimoxazole 2 tabs twice daily plus Metronidazole 400 mg three times daily x 5 days

Rehydrate and send stool sample to look for parasites, including Isospora and Cryptosporidium

If no improvement

Rehydrate +
If diarrhoea persists

Ciprofloxacin 500mg BD x 5 days

If Cryptosporidium, give Paromomycin 500 mg QID for 2 weeks If Isospora, give CTX 2 tabs QID for 10 days, then 2 tabs twice daily for another 3 weeks Enroll to start ARVs as soon as possible!

Note: CTX = cotrimoxazole. Always ensure good hydration; use IV fluids if necessary! Refer to hospital if: Bloody diarrhoea AND temperature above 38 degrees Celsius Or, signs of severe dehydration: poor urine output, confusion or drowsiness, hypotension

69

Diarrhoea is VERY common in HIV-infected adults and children. For management purposes, it is very important that the nurse or doctor make a distinction between acute and chronic diarrhoea.

Acute diarrhoea
Clinical presentation
Acute diarrhoea is characterised by: ore than 3 loose stools/day M A duration of less than 2 weeks Without significant weight loss Disappearing spontaneously or with appropriate treatment

Two syndromes are to be noted: 1. Gastroenteritic syndrome: simple diarrhoea caused by viruses, bacteria (E. coli), food poisoning (Staphylococcus), or Salmonella. 2. Dysenteric syndrome: painful, diarrhoea with mucous and/or blood, with rectal symptoms, caused by Shigella, Amoeba enterolytica, Campylobacter and some E. coli strains. Clinically check for fever and signs of dehydration (especially in children):
Gastro-intestinal Conditions

IMCI Classification of dehydration

Signs Severe dehydration (2 of the following signs) Lethargic or unconscious Sunken Poor or unable Some dehydration (2 of the following signs) Restless and irritable Sunken Eager, thirstily No visible dehydration Alert Not sunken Normal, not thirstily Returns immediately

Level of consciousness Sunken eyes Ability to drink Skin pinch (turgor)

Very slow return > 2 Returns slowly < 2 seconds seconds

Management
Rehydration This is crucial! Tell patient to drink as much as possible, and as often as possible. Oral rehydration salts (ORS) are best, but any fluid will do. Sugar Salt Solution (SSS) can be prepared according to the recipe below. If the person is unable to drink and/or severe vomiting is present, arrange for intravenous fluid.

70

Gastro-intestinal Conditions

ORS is prepared by dissolving the contents of one sachet into 1 litre of clean or boiled water. SSS can be prepared according to the following recipe: One litre of clean boiled water + half a teaspoon of salt + 8 teaspoons of sugar. It is also recommended to add some potassium if possible (for example, by adding some orange or grapefruit juice). Then give litre (1 full cup) every 15 minutes Make a new batch of ORS or SSS every day, and keep the ORS or SSS clean and cool. Nutritional advice Continue offering food, which is important especially for children (do not starve the patient!). No special diet is needed, but very spicy food or very oily food should be avoided. Try rice, potatoes, maize porridge, and bananas. Antibiotic therapy If the diarrhoea improves on its own within 1 week, then only rehydration and nutritional advice are necessary. If acute diarrhoea doesnt improve within 1 week, then empiric antibiotic therapy is needed as follows (empiric means that no lab studies, microbiology, or cultures are performed): If the person has frequent stools (> 6 per day), together with a high temperature and/or bad cramps, then give: otrimoxazole 480 mg 2 tablets twice daily x 5 days, AND C Metronidazole 400 mg three times daily x 5 days

If there is blood in the stools together with the above symptoms, or the diarrhoea is not improved with the above treatment, then give: ciprofloxacin 500 mg twice daily x 5 days

Children
Look for signs of dehydration and assess gravity as per IMCI guidelines Severe dehydration: 20 mg/kg Ringers lactate or Normal Saline rapidly. Refer urgently to hospital. Some dehydration: Give oral ORS 80 ml/kg over 4 hours. Increase the amount if the child wants more, and encourage the mother to continue breastfeeding where applicable, or to give any other fluids. For prevention of dehydration, caregiver needs to give 10 ml/kg of fluids after each loose stool:

71

Child age up to 2 years: 50-100 ml; Child age > 2 years: 100-200 ml Use Sugar salt solution, or if the child has been rehydrated for severe dehydration or some dehydration, use ORS

Zinc supplements (lessen the period of diarrhoea and stool frequency) Age < 6 months: 10 mg daily for 14 days; Age > 6 months: 20 mg daily

If blood in stool: Ciprofloxacin 15 mg/kg/dose twice daily for 3 days. If not on exclusive breast milk offer food-based fluids, e.g. soft porridge, maas (amasi), yoghurt, Sugar salt solution or ORS. Be cautious with rehydration in severely malnourished children.

REFER
Children with the following symptoms need URGENT referral: Lethargic/unconscious Eyes sunken Drink poorly/unable to drink Decrease in skin turgor
Gastro-intestinal Conditions

Chronic diarrhoea
Always think of TB since abdominal TB can cause chronic diarrhoea! HIV itself can directly cause chronic diarrhoea, but other causes need to be excluded first before blaming the diarrhoea on the HIV. On ARVs: didanosine (ddI), lopinavir/ritonavir (Aluvia and Kaletra) and ritonavir can cause loose stools, which are ongoing.

Clinical presentation
hronic diarrhoea is characterised by diarrhoea for more than 2 weeks and is C often associated with significant weight loss.

Management
Non specific treatment: ehydration as described above. R Adults iwth unexplained chronic diarrhoea > one month are in no less than clinical stage 3. Start cotrimoxazole prophylaxis. If the CD4 count is less than 200 or less than National criteria for initiation (which it often is), then enrol for ARVs. Nutritional advice as described above. If on ARVs with ongoing diarrhoea and weight loss, refer for further investigation

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Gastro-intestinal Conditions

Specific Treatment: 1. If the patient has not been treated at all for diarrhoea: Empiric antibiotic treatment with high-dose cotrimoxazole and metronidazole as above (or ciprofloxacin as described) Check response to treatment after 3 days.

2. If the diarrhoea persists: send two stool samples for microscopy, looking for coccidian parasites (especially Isospora and Cryptosporidium). 3. Treat any infection that shows up in the stool investigation report: Isosporiasis: give cotrimoxazole 480 mg 2 tablets four times daily for 10 days, then 2 tablets twice daily for at least 3 weeks. Cryptosporidiosis: rehydration therapy and nutritional advice as above; can try paromomycin if available (but expensive) Since both represent clinical stage 4, start counselling about ARVs!

4. If the chronic diarrhoea has still not improved and the patient is severely immunosuppressed: Start ARVs as soon as possible! In the meantime consider: Microsporidiosis: try albendazole 400 mg daily for 2 weeks (if available). CMV colitis or atypical mycobacterium infection, both of which can only be diagnosed at a referral hospital. 5. In a patient who has recently started a LPV/r based regimen, diarrhea (especially if not severe) might be drug-induced (LPV and Ritonavir): in this case, reassure the patient and treat symptomatically (most of the time, it improves without changing treatment). If it does not, refer to doctor (changing LPV to ATV can be considered).

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Special note about anti-diarrhoeal drugs

Anti-diarrhoeal drugs must be used cautiously as they slow the motility of the intestinal tract which may result in harmful bacteria being retained (or kept inside). The syndromic management of diarrhoea must be completed before considering such anti-diarrhoeal drugs. In the event of a poor response to syndromic management, the following anti-diarrhoeal drugs can be used (while enrolling the patient for ARVs). But prescribing the following drugs requires more frequent patient follow-up (every 2-3 days): Loperamide 2 mg tablet after each episode of diarrhoea, up to 6 tablets a day, or Codeine phosphate 30 mg, 1 tablet three times daily

Children
Management as above. No pathogen identified: CTX 40+8 mg/kg/dose three times daily + metronidazole 10 mg/kg/dose three times daily for 5-7 days. Children with unexplained persistent diarrhoea for 14 days or more are in no less than clinical stage 3. Start cotrimoxazole prophylaxis and assess eligibility for ART.

Gastro-intestinal Conditions

REMEMBER

Always assess children with acute or chronic diarrhea for other infections: UTIs, ear infections, pneumonia and sepsis can be associated with diarrhea.

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Abdominal pain

Gastro-intestinal Conditions

Localized Consider Consider

Generalized

Upper Abdominal Constipation Other OIs (NTM, CMV, histoplasmosis) Diet, fluids, laxatives Cancers: Lymphoma, KS

Lower abdominal

Abdominal TB

On d4t (or AZT): Lactic Acidosis or symptomatic hyperlactatemia.

Consider

Epigastric: peptic

Pregnancy!

be felt as abdominal pain, especially in the young child! See Algorithm 16 (page 177). Refer for abdominal ultrasound, biopsy

ulcers, GERD,

Algorithm 6: Approach to Abdominal pain

Pancreatitis; RUQ:

UTI, PID, STI

Hepatitis cholecystitis

See Algorithms 9 &

Obtain good

10 (pages 126127).

clinical history!

Pregnancy test

Take blood for ALT

Note: Also remember that conditions other than GI conditions, such as pneumonia may

and lipase

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Abdominal pain (No diarrhoea)

See Algorithm 6 on previous page for an approach to abdominal pain.

REFER
Recognise the severely ill client: HIV with abdominal pain and one or more of the following signs: Peritonitis (guarding or rigidity on abdominal examination) Jaundice If on ARVs, any sign of lactic acidosis: See algorithm 16 (page 177). Temperature 38 C. Refer same day to hospital
Gastro-intestinal Conditions

Always examine the lungs of a young child who complains of abdominal pain! A child with pneumonia often complains of belly pain.

REMEMBER

Hepatitis B co-infection
Hepatitis B infection is a serious disease caused by a virus called hepatitis B virus (HBV). HBV infects the liver causing acute +/- chronic liver problems. For the HIV positive co-infected person, it can also complicate management with ARVs. Many National Departments of Health, including South Africas, have now added Hepatitis B vaccination to their routine Vaccination Program for children.

Diagnosis
A positive Hepatitis B surface antigen test (HBsAg+) means that a client has active hepatitis B disease. In SA, routine testing is no longer necessary for clients who initiate ARVs, since the usual first line regimen now includes TDF /3TC (or FTC), which are indicated for all HBsAg+ individuals. HBsAg testing should be considered for clients with a baseline ALT > 40, and for any individual who is being considered for stopping or not starting TDF. There is a difference between the antibody test and the antigen test. A positive hepatitis B antibody test could mean that: a) the individual has been infected with

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Gastro-intestinal Conditions

hepatitis B at some time in the past, or b) he/she was vaccinated against hepatitis B. Having antibodies for hepatitis B does not mean that the person has chronic hepatitis B disease. If the HBsAg test comes back as weakly positive, the test should be repeated.

Management
atients who need ARVs or are on ARVs and have a positive HBsAg need to be P treated with tenofovir (TDF) and lamivudine (3TC). TDF can occasionally affect the kidneys. It is contra-indicated if the creatinine clearance (CrCl) < 50 ml/min. Serum creatinine is not a good marker of the kidney function. Instead the CrCl should be calculated with the equation of Cockcroft-Gault:

CrCl (ml/min) =

weight (kg) x (140 age) 0.82 x serum creatinine (mol/L)

For females, multiply this result by 0.85

In SA, TDF is not recommended for use in children less than 15 years due to its effect on bone mineral density. Clients to be started on TDF need: A baseline serum creatinine and the calculation of CrCl (If < 50 ml/min, specialist advice is required). CrCl follow up at 3, 6, and 12 months, then yearly.

When switching patients with hepatitis B infection to second-line regimens, they need to remain on TDF and 3TC! Stopping TDF could cause a severe flare of the hepatitis. Close monitoring for worsening of hepatitis B status should be done.

REMEMBER
Always check the creatinine clearance before starting TDF. Only looking at the serum creatinine result is not enough (especially for clients aged > 50 years, those who weigh < 50 kg, or those with serum creatinine > 100.) Patients with chronic hepatitis B need to stay on TDF and 3TC, even if they are switched to another regimen.

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Notes
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Gastro-intestinal Conditions

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Gastro-intestinal Conditions

Notes
................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................ ................................................................................................................................................................................

Pulmonary Conditions

Mariella Furrer/THINK pictures

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Acute Chronic
>2 wks

Pulmonary Conditions

< 2 wks

Bacterial Pneumonia TB Any CD4 Cough (dry or productive) Respiratory rate can be normal Enquire about close TB contact

PCP

Chronic Lung Diseases (i.e., COPD in the elderly, LIP in children) +/- associated with a high temperature For LIP, look for: bilateral parotid gland enlargement, hepatosplenomegaly and clubbing of the digits KS Look for skin lesions

Any CD4

Most common in severely immune-

Productive cough +/- blood

depressed, especially if not on

High temp

cotrimoxazole prophylaxis.

+/- dyspnoea while walking

Dry cough, hypoxia,

+/- unilateral chest pain

+/- high temp

Acute Bronchitis

High respiratory rate

Figure 4: Pulmonary conditions not to miss!

Respiratory rate is normal

Subacute presentation but may

worsen quickly!

Watch for PCP in HIV exposed

or infected infants

Management: see page 105108 Management: see page 8395

Management: see

Note in chart if client was on CTX

For LIP: see page 108 KS: see page109

page 103105

when she/he developed PCP

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Introduction to Pulmonary Conditions:

Common pulmonary diagnoses
The three most common pulmonary diagnoses in HIV-positive people are: ulmonary Tuberculosis (PTB) P Lower Respiratory Tract Infections (LRTIs) Acute bronchitis Bacterial pneumonia

Pneumocystis jiroveci pneumonia (PCP)

Clinical presentation
But of course, people dont come in and tell us their diagnosis. They come to us with symptoms. As always, it is important to take a good history, especially when a person is sick. If someone comes in with respiratory symptoms, make sure to identify all of the following worrisome respiratory symptoms and signs (Also see Appendix 14): ough C Dyspnoea (shortness of breath) Tachypnoea (fast breathing determined by examination) High temperature
Pulmonary Conditions

Likely diagnoses according to presentation (always ask how long symptoms have been going on): cute onset (< 2 weeks): A Acute bronchitis Bacterial pneumonia Pneumocystis jiroveci pneumonia (PCP), which has a subacute onset, but eventual rapid deterioration. Chronic onset (> 2 weeks): Pulmonary TB Pulmonary Kaposi sarcoma Chronic Obstructive Pulmonary Disease (COPD)

It is important to recognize the severely ill client. Look out for the TB suspect with one or more of the following signs: espiratory rate 30 breaths/minute R Breathlessness at rest or while talking

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Pulmonary Conditions

Prominent use of the breathing muscles Agitated or confused Unable to walk unaided

Management
If the client is severely ill, he/she will need rapid treatment: ive oxygen (40% face-mask oxygen or at least 4 L/min via nasal prongs). G Ceftriaxone 1g IM/IV (If unavailable, amoxicillin 1g orally. If penicillin allergic give erythromycin 500mg orally). Take first sputum for AFBs and arrange follow up. Refer same day to hospital.

REMEMBER TB and HIV together = Double-Trouble!

The clinical presentation and the diagnostic approach are different in HIV-positive patients who have active TB. As an HIV-positive persons immune system weakens, active TB presents differently. TB is more often located outside the lungs in HIV-positive people. This is known as extra-pulmonary TB (or EPTB). Active TB is more difficult to diagnose in HIV-positive people. The nurse or doctor has to frequently order investigations other than sputum smears to prove the diagnosis of TB. Sputum smears are more likely to be negative in HIV-positive clients with active TB!!! Since their immune systems are weaker, there is less cavityformation in the lungs. As a result, HIV-positive people tend to cough up fewer TB germs, so their smears are often reported as negative. Therefore, never tell HIV-positive clients with symptoms of TB (but negative smear results) that they do not have TB! Despite the negative smear results, these clients almost certainly still have TB. We just have to do other tests to prove it!!! Once diagnosed, the treatment of TB is the same whether a person is HIV-positive or negative.

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REMEMBER TB and HIV services should be INTEGRATED

in settings where HIV and TB are common
Approximately ten percent of HIV-positive people get TB every year! And up to 70% of those receiving treatment for TB are HIV-positive (whether they know it or not) in these settings. Integration of HIV and TB services would help reduce the number of TB deaths in HIV patients by reducing diagnostic delay of TB. Integration would also reduce the number of TB patients dying from other HIVrelated infections, by encouraging HIV testing in TB patients and allowing earlier comprehensive HIV treatment of those who are HIV-positive. All people receiving TB treatment should get an HIV test! All HIV positive people with TB should get a CD4 count! All HIV-positive people with pulmonary or lymph node TB (the latter considered in S.A. to be clinical stage 3) and CD4 350 are eligible for ARVs. All HIV-positive people with EPTB (except isolated lymph node TB), or MDR/XDR TB, are eligible for ARVs irrespective of the CD4 count result.

Pulmonary Tuberculosis (TB of the lungs = PTB)

When someone has a chronic cough, PTB is the first diagnosis to think of and always needs to be ruled out! TB is caused by the organism Mycobacterium tuberculosis. In HIV-positive patients, a diagnosis of pulmonary TB means that the adult or child is in stage 3 of HIV infection (see Appendices 1 and 2). Pulmonary symptoms of TB together with pleural effusion or miliary pattern on chest x-ray are actually considered to be extra-pulmonary TB (EPTB). PTB with pleural effusion or miliary TB means the person is in Clinical stage 4.

Pulmonary Conditions

Clinical presentation
Typical presentation The following symptoms usually occur in HIV-positive patients with mild immunodeficiency (high CD4 counts). They are similar to the TB symptoms experienced by HIV-negative patients with PTB: hronic cough 2-3 weeks, not fully responding to antibiotics C Recent unintentional weight loss ( 1.5kg within 4 weeks) Drenching night sweats Fever 2 weeks Chest pain > 14 days

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Pulmonary Conditions

Loss of appetite and weight loss General weakness and tiredness Sometimes haemoptysis (flecks of blood in the sputum when coughing) Known TB contact

Atypical presentation With more advanced immunodeficiency (low CD4 counts), the HIV-positive patient may present with different symptoms: eneral malaise and weakness G Looks really sick Significant weight loss (> 10% of previous body weight) Less coughing, which tends to be a dry cough Shortness of breath Severe anaemia Disseminated TB and extra-pulmonary TB (meaning involvement of any organ outside of the lungs); adults and children with EPTB are in stage 4 of HIV infection (see Appendices 1 and 2). The exception is isolated lymph node TB which is only a stage 3 condition for a child (and for adults in S.A.).

Clinical Examination
Always perform a good physical examination to check for pleural effusion or enlarged lymph nodes (> 2 cm), which are both strongly suggestive of active TB. If you see a patient with a large or chronically infected lymph node in the neck, armpits, or groin, which does not respond to antibiotics, this is probably TB! A fine needle aspiration biopsy (FNAB) should be performed without delay (see Appendix 29).

Diagnosis of an HIV-infected person with symptoms of PTB

1. Send 2-3 sputum samples for TB microscopy (smears). Make sure the patient provides sputum from the lungs, and not saliva from the mouth! Early morning sputum is best (see Appendix 20). 2. While waiting for the smear results, prescribe an antibiotic to cover for any bacterial cause of the chronic cough (Amoxicillin 500-1000 mg 3 times daily or erythromycin 500 mg 4 times daily if penicillin allergic). Note the patients score on the Karnofsky performance scale (Appendix 15). 3. If the smears are positive, start TB treatment. 4. If the smear results return negative and the person still has symptoms of TB (despite the antibiotic), follow the Smear-negative algorithm

85

(see page 86). Ask for: hest x-ray C One more sputum sample for TB culture. This results could take up to 6 weeks before coming back. C-reactive protein (CRP) blood test. This is a non-specific but useful blood test that tells us how much inflammation is going on in a persons body. When the CRP is raised, it suggests inflammation, which might be active TB in a person with symptoms of TB. Consider this possibility especially in a patient whose CRP remains elevated after a course of antibiotics. A baseline haemoglobin can also be done. Patients with TB are often anaemic. Consider a needle biopsy of any enlarged lymph nodes. Consider a pleural tap if a pleural effusion is present in order to exclude empyema. 5. If the chest x-ray and clinical picture are consistent with active TB, then the patient needs to be started on TB medication, and monitored. 6. Dont forget to start all TB patients on cotrimoxazole prophylaxis (Bactrim) to prevent other OIs!
Pulmonary Conditions

Monitoring
While empiric TB treatment is being given, the patient must be monitored every 1-2 weeks for improvement. Response to treatment is measured by the following: mprovement of general condition (less sick?) I Karnofsky performance score (see Appendix 15) Improvement of symptoms (cough, night sweats, and appetite) Weight gain (another reason to check weight every visit) Decreased C-reactive protein (CRP) after 2 weeks Increased haemoglobin after 1-2 months

If the patient is not improving on empiric TB meds, then refer to the doctor for assessment. If the chest x-ray is not consistent with active TB, but the patient is still sick, that is another reason to refer. NB: TB drugs interact with several other medications. Be particularly careful if the patient is also on warfarin, oral contraceptives, or antiretrovirals.

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Pulmonary Conditions

patients suspected of having TB (Pulmonary presentation with or without enlarged lymph nodes).
Pulmonary presentation= Cough > 14 days with or without night sweats, recent weight loss, or deteriorating level of function Sputum smear x 2 Needle Biopsy if lymph node > 2 cm (send for TB smear) Amoxicillin 500 mg TDS x 10 days (or erythromycin if allergic to penicillin)

Algorithm 7: Smear-negative Algorithm for management of HIV

If large Pleural effusion is present, Doctor to perform pleural tap in order to exclude empyema. Send sample for protein, ADA, cell count and TB smear (and culture if possible). Consider PCP if RR > 30, cyanosed, and ground glass bilateral infiltrate on Chest x-ray.

Symptoms and signs resolved, weight stable and smears negative

No sputum produced (dry cough) or smears negative and patient remains symptomatic Smear(s) positive* or granulomas on Needle biopsy

Chest X-ray, blood tests (CRP and Hb), Karnofsky score and 3rd sputum for culture

Routine monitoring * If only one smear is positive then perform CXR and send 3rd sputum for TB smear (and culture if possible) for further evidence, but start TB treatment regardless.

Culture positive

Start TB Treatment if clinical picture and Chest X-ray are consistent with active TB

Chest X-ray normal or not consistent with active TB

Monitoring on TB treatment: symptoms, weight, temperature, Karnofsky score, repeat CRP (after 2 weeks) and Hb (after 1 month)

TB treatment Complete Regimen 1 or 2

Favourable response

Poor response at 8 weeks (or earlier if deteriorating)

Refer to doctor (or to Hospital if sick and needs admission)

Source: P Saranchuk, A Boulle, K Hilderbrand, D Coetzee, M Bedelu, G van Cutsem, G Meintjes. Evaluation of a diagnostic algorithm for smear-negative pulmonary tuberculosis in HIV-infected adults. S Afr Med J 2007; 97: 517-523.

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TB Management
TB Treatment regimens Treatment for TB is different for new cases and retreatment cases. New cases are patients who never had TB before. They have to take TB treatment for 6 months, consisting of 2 months of intensive phase with Rifafour (RHZE) and 4 months of continuation phase with Rifinah or Rimactazid (RH). Sputum needs to be checked at 2 and 5 months (in all cases of smear-positive PTB or smear-negative/ culture-positive PTB).* Retreatment cases are patients who were treated for TB before. Their treatment lasts 8 months and consists of 2 months of Rifafour plus streptomycin injections, 1 month of Rifafour, and 5 months of Rifinah or Rimactazid plus ethambutol. Sputum needs to be checked at 3 and 7 months (in all cases of smear-positive PTB or smear-negative/culture-positive PTB).*

Table 3. Frequency of sputum smear/culture follow-up in patients with TB

End of initial phase New patient Smear-positive PTB Smear-negative, culture-positive PTB 7th week, 2 sputa for smear1 7th week, 2 sputa for smear1 Retreatment 11th week, 2 sputa for smear1 11th week, 2 sputa for smear1 End of continuation phase New patient Retreatment
Pulmonary Conditions

5th month, 2 7th month, 2 sputa for smear1 sputa for smear1 5th month, 2 sputa for smear AND 1 for culture2 7th month, 2 sputa for smear AND 1 for culture2

Smear-negative, Repeat CXR if initially culture negative diagnosed using it TB (including EPTB) Notes: 1. Ask for culture and DST if smear positive 2. Ask for DST if culture still positive

Monitor clinically, once CXR has shown improvement3

3. Its generally useful to have an end of treatment CXR, for comparison, in case symptoms recur * If sputum culture is positive for non-tuberculous mycolacteria (NTM), theres no need to monitor the sputum culture, as long as the patient is improving clinically on standard TB treatment. If no improvement: refer.

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Pulmonary Conditions

Table 4. Regimen 1: New cases, age above 8 years and

adults
Pre-treatment weight Intensive phase (2 months) RHZE (150/75/400/275) (Rifafour) 30-37kg 38-54kg 55-70kg >71kg 2 tablets daily 3 tablets daily 4 tablets daily 5 tablets daily Continuation phase (4 months) RH (150mg; 75mg) 2 tablets daily 3 tablets daily 2 tablets daily 2 tablets daily RH (300mg; 150mg)

and adults (If the facility is able to, streptomycin should be given at weekends too)
Preweight Intensive phase Seven times a week RHZE (Rifafour) 30-37kg 38-54kg 55-70kg >71kg Streptomycin Injection 3rd month initial phase RHZE (Rifafour) Continuation phase (4 months) Seven times a week treatment (2 months)

Table 5. Regimen 2: Re-treatment cases, age above 8 years

RH (150/ E RH (300/ E 75mg) (400mg) 150mg) (400mg)

2 tablets 0.5g IM

2 tablets 2 tablets 2 tablets

3 tablets 0.75g IM 3 tablets 3 tablets 2 tablets 4 tablets 1g IM 5 tablets 1g IM 4 tablets 5 tablets 2 tablets 3 tablets 2 tablets 3 tablets

Streptomycin is contraindicated in: pregnant women, patients > 65 years and/or patients with pre-existing renal disease (unless the dosage is adapted to the CrCl of the patient). Since Streptomycin and TDF can both cause renal toxicity, it is recommended that they not be given together. Discuss with doctor if a patient on TDF needs streptomycin.

89

cases)

Table 6. Regimen 3: Children < 8 years (Uncomplicated TB

Weight 2 months initial phase 4 months continuation phase RHZ 60,30,150 2-2.9 kg 3- 5.9 kg 6- 8.9 kg 9-11.9 kg 12-14.9 kg 15-19.9 kg 20-24.9 kg 25-29.9 kg 30-35.9 kg Half a tablet 1 tablet One and a half tablet 2 tablets Two and a half tablets 3 tablets 4 tablets 5 tablets 6 tablets RH 60,30 Half a tablet 1 tablet One and a half tablet 2 tablets Two and a half tablets 3 tablets 4 tablets 5 tablets 6 tablets
Pulmonary Conditions

(RHZ = Rifampicin Isoniazid Pyrazinamide) Note: In South Africa, regimen 3 is for children < 8 years who have uncomplicated PTB, lymph node TB or TB pleural effusion. Children < 8 years who are smear positive PTB cases or smear negative re-treatment cases are treated with regimen 1, adding ethambutol 20 mg/kg/day (range 15-25 mg/kg/day) during the first 2 months of treatment. Children < 8 years who are smear positive re-treatment cases are treated with regimen 2 (SA National TB Guidelines 2008). For all patients receiving INH, give pyridoxine (vitamin B6) to avoid peripheral neuropathy: adults and children > 5 years: 25 mg OD children < 5 years: 12.5 mg OD

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Pulmonary Conditions

TB treatment and ARVs 1. If an adult or child already on ARVs is diagnosed with TB: The ARV regimen may need to be modified according to the Table below.

Table 7. Changes to ARV regimen while on treatment for TB

Current regimen includes NVP EFV Non pregnant adults Pregnant women in 2nd or 3rd trimester Children > 3 years and > 10 kg Double dose LPV/r (see Appendix 7) LPV/r super-boosted with additional ritonavir (see Appendices 8 and 9) LPV/r Double dose of LPV/r (see Appendix 7) LPV/r boosted with additional ritonavir (see Appendices 8 and 9) D4T Consider change to TDF unless patient needs streptomycin or treatment for DR TB with Amikacin or Capreomycin. Patients 15 years and over (provided CrCl > 50) Adults Older children (> 5 years) Children < 5 years (refer to doctor) Pregnant women in 1st trimester Children < 3 years or < 10 kg Change drug to Patient group

Note: Continue double dose LPV/r (or additional ritonavir) for 2 weeks after stopping the rifampicin-containing TB regimen. Consider changing D4T to TDF to

prevent peripheral neuropathy. Do not change D4T to TDF if patient is suspected of virological failure.
2. If TB infection is present before being assessed for ARVs: For the choice of ARV regimen, refer to Appendix 7 (adults) or 8 (children). See below for the timing of ARV initiation if TB is present before being assessed for ARVs.

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Adults

Table 8: Timing of ARV initiation after the start of treatment for TB

Clinical Situation Timing of ARV initiation after the start of TB treatment All cases of MDR/XDR TB Pregnant women 2 weeks Initiate within 2-4 weeks (2 weeks if CD4 < 50). If CD4 count is higher and clinically stable, try to wait until the end of the 1st trimester (then initiate with EFV). Since WHO classifies those with EPTB as clinical stage 4, initiate ART once patient is stable on TB treatment, usually within 2-4 weeks. Note that an adaptation has been made in South Africa, where adults having isolated lymph node TB are still considered to be in clinical stage 3 (see Appendix 1). Initiate ART once patient is stable on TB treatment, usually within 2-4 weeks. Since CD4 > 350, the person is not eligible for ART. Repeat CD4 and reassess need for ARVs at the end of TB treatment. Initiate ART once patient is stable on TB treatment, usually within 2-4 weeks.
Pulmonary Conditions

All cases of EPTB (except isolated lymph node TB)

CD4 < 350 and pulmonary TB or isolated lymph node TB CD4 > 350 and pulmonary TB or isolated lymph node TB CD4 > 350 and EPTB (except isolated lymph node TB) or stage 4 condition other than TB Children

All children with TB meet criteria for ART Begin ART as soon as TB drugs are tolerated (2-8 weeks into treatment) irrespective of CD4 count and clinical stage. Start after 2 weeks in case of MDR/ XDR TB, or a very low CD4 (ie < 5-10 %) If the child with lymph node or pulmonary TB is relatively well, and has a high CD4 count (> 25 %), delaying ART initiation beyond 8 weeks may be considered to avoid a high pill burden and potential drug interactions, provided the child is closely monitored. Discuss with doctor.

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Pulmonary Conditions

3. If TB treatment and ARVs are being taken at the same time Make sure that NVP is changed to EFV, or the LPV/r dose is doubled (or super-boosted with additional ritonavir). This should be continued until 2 weeks after the completion of treatment for TB. Monitor for drug interactions Monitor for side effects, especially hepatitis Refer to the doctor if either is suspected Since the patient will be taking a large number of tablets, ensure adequate counseling is done in order to maintain adherence

Special considerations for TB/HIV co-infected children

Active screening
Active screening for TB in children is essential: lways ask about contact with an adult with Pulmonary TB A Common presenting symptoms Persistent cough >14 days Fever > 38 0C for over 1 week (after excluding other causes of fever) Weight loss (dont forget to look at the Road to Health card!) Unusual fatigue

A visible mass in the neck, not responding to a course of antibiotics and without a visible local cause probably represents lymph node TB

Diagnosis
Diagnosis of TB in children is difficult, especially in the HIV positive child. Other pulmonary conditions may present with symptoms similar to TB (LIP, bacterial pneumonia, fungal pneumonia, etc). Also, if the child is able to produce sputum, it is often paucibacillary (with few germs) so sputum smears are often negative. So, we need to use many pieces of information to make the diagnosis of TB in a child: contact history and clinical presentation are most important. Other investigations may also help: a child over 5 years is generally old enough to try to produce sputum; induced sputum (preferred) or gastric aspirate could help in the younger child. Depending on local resources, CXR, TB skin testing and fine needle aspirate (FNA) of large lymph nodes should be done. Induced sputum or gastric aspirates help increase the yield of sputum production (see below) in facilities where there are trained staff to do these.

93

A swelling (raised, thickened area) of 5 mm or more on a TB skin test in an HIV positive child is a positive test, and tells us that the child has been infected with TB. It does not necessarily mean that the child has active TB disease. However, this test result is another clue that we can use to help us make the diagnosis. Remember, though, that a negative test does not exclude TB. CXRs are hard to interpret in the HIV positive child, and can be normal in up to

1/3 of HIV-infected children with active TB. The eye of an experienced clinician is
often needed to make a diagnosis and TB should not be diagnosed from the CXR alone. The most common feature on x-ray is hilar lymphadenopathy. Other features may also be present, including: alveolar consolidation, cavitation or miliary pattern. Note: a miliary pattern in a non-sick looking child most likely means the child has lymphoid interstitial pneumonia (LIP), not TB. Fine needle aspirate of lymph nodes >= 1 cm should be done when indicated. This is then mounted on a slide and sent for microscopy; AFB or granulomas can be diagnostic.

To improve yield of sputum production, one can use one of the following (in facilities where conditions allow):
Induced sputum collection- first give a bronchodilator (inhalant 200mcg) then nebulize with hypertonic saline using an ultrasonic nebulizer. An older child can then expectorate the sputum but if unable, suctioning the pharynx also has a good yield. Send for microscopy and culture. Gastric washing or gastric aspirates are well used procedures. Requires the child to fast over night. Send for microscopy and culture.

Pulmonary Conditions

REMEMBER
Remember to keep a high index of suspicion for TB in a child. In other words, if you think the child might have TB, he/she should be investigated further. If CXRs are not available, and the child has chronic symptoms and a known TB contact, refer him/her for TB treatment (sputum collection should be attempted whenever possible). If the HIV positive child has persistent symptoms after a course of antibiotics, refer him/her to the doctor for further evaluation, even if there is no known history of contact and/or TB skin test is negative.

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Pulmonary Conditions

Management:
Management of TB is the same as for HIV-negative children.

Children with EPTB may require prolonged treatment of at least 9 months and 4 drugs (including ethambutol) during the intensive phase of treatment.
In-patient management should be considered for children that are severely affected. Nutritional support is very important especially if the child is malnourished

The child needs CTX prophylaxis and enrolment for ARVs (see page 91 for timing of ART initiation). Pyridoxine: give 12.5 mg daily for those < 5 years, and 25 mg daily for those > 5 years.

adequate therapy, the most important questions to ask are:

Is the drug dosage correct? Is the child adherent? Was the child severely malnourished?

REMEMBER If the childs symptoms worsen despite

Is there a reason to suspect drug resistant TB (index case has known drug resistant TB, is a relapse case, or is also not responding to therapy)?
Has the child developed IRIS (if on ARVs)? Is there another reason for the childs illness, other than or in addition to TB?

Refer for assessment

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REFER
Danger signs requiring urgent hospital referral Severe respiratory distress (TB pneumonia with/without bacterial super infection) Severe wheezing not responding to bronchodilators (signs of severe airway compression) Headache (especially if accompanied by vomiting), irritability, drowsiness, neck stiffness and convulsions (signs of TB meningitis) Big liver and spleen (signs of disseminated TB) Breathlessness and peripheral oedema (signs of pericardial effusion, fluid around the heart) Distended abdomen with ascites (signs of abdominal TB) Acute angulation (bending) of the spine (sign of TB in the spine)

Prevention of TB
INH preventive therapy in the adult (TB prophylaxis, see also page 20)
TB can be prevented in HIV-positive patients, especially if there has been recent close contact with someone else coughing with active TB. This is done by prescribing a single TB medication called Isoniazid (INH) for 6 months. Giving INH 300 mg daily for 6 months reduces the risk of developing active TB by 60% within the next 2 years. The efficacy, though, has not been established in those patients already on ARVs, so for them its not recommended. But before using INH, we must be certain that the person does not have active TB. Or else we may be making things worse, as giving INH monotherapy to a person with active TB would promote resistance of the TB organism against INH! TB prophylaxis with INH is indicated for persons in whom the following applies: he patient is infected with HIV and not on ARVs. T Had contact with active TB case, or has a positive TB skin test (TST). Active TB has been excluded (clinically, by CXR and/or sputum smears). In other words: the patient must be healthy. Always exclude active TB before initiating INH prophylaxis. Pregnancy is not a contraindication for INH prophylaxis. Always remember to associate Pyridoxine (vitamin B6).
Pulmonary Conditions

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Pulmonary Conditions

INH preventive therapy in the child

outine INH prophylaxis in HIV+ children is not currently recommended in S.A. R However, WHO and MSF recommend giving INH routinely to all HIV+ (6 months of INH every 3 years) after exclusion of active TB. Babies born to a mother with infectious pulmonary TB should not receive BCG vaccination at birth. Instead, if asymptomatic, they should be given INH prophylaxis 10 mg/kg/day for 6 months. A mother with pulmonary TB (smear-negative or positive) is considered infectious if she has been on TB treatment for less than 2 months prior to delivery, or, for smear-positive cases, if a negative smear has not yet been obtained by the time the baby is born. All HIV infected children of any age with a documented TB exposure should be screened according to Algorithm 8 on page 98. INH preventive therapy 10 mg/kg/day for 6 months should be given if the child is asymptomatic. (Non HIV positive siblings < 5 years of age should also receive prophylaxis if asymptomatic). If the source case is resistant to INH only, rifampicin (10-15 mg/kg daily) prophylaxis should be given for 6 months. A symptomatic child should be investigated for TB and not receive INH prophylaxis. Children on INH prophylaxis should receive pyridoxine to avoid PN ( > 5 years 25 mg OD; < 5 years 12.5 mg OD)

Table 9. Dosage recommendations for INH preventive

therapy in children
Body weight 2-3.4 kg 3.5- 6.9 kg 7- 9.9 kg 10- 14.9 kg 15- 19.9 kg 20 -24.9 kg 25- 29.9 kg 30 kg Daily isoniazid (INH) 100 mg tablet One quarter of tablet One half tablet 1 tab 1 tab and one quarter 1 tab and one half 2 tabs 2 tabs and one half 3 tabs

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i
1.

TB infection control refers to what can be done to reduce the transmission of TB. Remember that everyone is responsible for TB infection control!
Administrative controls. These are the most important and include: Prompt identification of infectious TB cases Physical separation of patients known or suspected of having TB

2. Environmental controls Maximize natural ventilation Avoid being downwind from a patient

3. Personal respiratory protection Patients to wear surgical masks Staff to wear N 95 respirator masks (note that surgical masks do not

protect against TB).

Pulmonary Conditions

REMEMBER The three Is to reduce the burden of TB

among people living with HIV:
1. Intensified case finding for TB 2. Isoniazid preventive therapy 3. Infection control

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Pulmonary Conditions

Algorithm 8: Screening of an HIV infected child with

Documented TB exposure in HIV infected child

documented TB exposure (SA National TB guidelines 2008)

Close contact with an adult or adolescent with pulmonary TB or a child with smear-positive TB Close contact is defined as any household contact or contact outside the household that is of sufficient duration to pose a high risk of infection

No current symptoms or signs

Symptoms or signs present

Investigate for TB (sputum smear, CXR, TST depending on availability

Not TB

TB diagnosed

Follow up after 1-2 weeks

Child is well Preventive INH 10 mg/kg/ day for 6 months (see table page 96) Symptoms persist

Treat for TB Enter into TB register

Observe for symptoms Refer if symptoms indicative of TB Refer

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Drug Resistant Tuberculosis (DR TB)

If someone on TB treatment has been adherent to their treatment but is not improving, the first diagnosis to think of and to rule out is Drug Resistant TB.

Classification of drug resistant TB

Drug resistant TB is classified into 4 categories: 1. Mono Resistant: Resistance to one of the first line drugs: Ethambutol (E), Rifampicin* (R), Isoniazid (H), Pyrazinamide (Z) 2. Poly Resistant: Resistance to two or more of first line drugs but not R and H together (see next definition) 3. MDR: Resistance to R and H 4. XDR: Resistance to R, H and one or more of the injectable drugs (capreomycin, kanamycin, amikacin) and any of the fluoroquinolones (e.g. ofloxacin) During the rest of this section, we will simply talk about drug resistant TB (DR TB) by which we mean at least rifampicin resistance.

Clinical presentation
What are the symptoms of DR TB? The symptoms of DR TB are the same as those of Drug Sensitive TB (DS TB). Patients may present with cough, weight loss, fatigue, night sweats, chest pain and/ or more atypical symptoms if they are HIV +ve with advanced immunodeficiency. Who gets DR TB? Transmission of DR TB is the same as drug sensitive TB. Anyone can get DR but certain people are more at risk. Those at increased risk of getting DR TB include: hose with a history of TB drug use: T Relapse Return after default Failure of treatment (greatest risk) History of using poor or unknown quality of drugs History of other medications that interfere with TB drug absorption.

Pulmonary Conditions

Contact of someone with DR TB. HIV (increase risk for all TB) and other chronic diseases such as diabetes mellitus. Health Care Workers, laboratory workers, prisoners and prison guards, miners.

* Note that Rifampicin mono-resistance is treated similarly to a case of MDR TB

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Pulmonary Conditions

Assessing the patient for DR TB It is important to ask the patient about previous episodes of TB and if they completed treatment or defaulted. It is also important to know if they have a history of exposure to DR TB or any chronic conditions such as HIV infection, diabetes mellitus, renal disease, malignancies or chronic malabsorption syndrome.

How do we diagnose DR TB?

DR TB is a laboratory diagnosis, however it is often suspected clinically. When a patient is suspected of DR TB, sputum is sent for smear, culture and drug sensitivity testing (DST). It is very important that the patient is instructed on how to give a good sputum specimen; otherwise you may just be submitting saliva to the laboratory. (See Appendix 20 for instructions on obtaining a sputum sample). Smear Smear microscopy cannot distinguish between drug sensitive or drug resistant TB, however it can evaluate the infectiousness of the patient. It is generally agreed upon that patients who are smear positive are more infectious than patients who are smear negative. However, one needs to remember that smear negative patients may also be infectious and transmit TB. Culture It takes many weeks to culture the TB mycobacterium, sometimes months. During this time if the patient is deteriorating clinically, refer to the doctor for further evaluation and management. Drug Sensitivity Testing (DST) DST is a laboratory test that identifies the TB drugs that the mycobacterium is sensitive and/or resistant to. If 1st line DST is requested, the laboratory will test resistance to Rifampicin and Isoniazid. If Rifampicin resistance is diagnosed, the laboratory will test for resistance to: ethambutol, ofloxacin, ethionamide, and Amikacin. DST results to these drugs may take up to 2 months to be reported. (NHLS states 100% cross-resistance between Kanamycin and Amikacin). Whose sputum do we send for smear, culture and DST (South African Guidelines)? ll re-treatment TB cases A Patients on TB treatment who remain sputum smear positive after 2 months (new cases) or three months (re treatment cases) of first line treatment. Symptomatic close contacts of confirmed DR TB cases.

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Symptomatic individuals from known high risk groups, including health care workers, laboratory workers, prisoners, miners (at the time of writing, HIV infection itself, is not considered an independent risk factor for DR TB screening in SA guidelines).

Hospitalization vs. Treatment at the clinics for DR TB? In Khayelitsha, MSF, City and Province are piloting a decentralized model of DR TB care. Once a patient is diagnosed with DR TB, he/she may be started on treatment by the Clinic TB Doctor. If the patient requires admission (very ill, social situation, behavioural problems) then the patient will be admitted to either BCH or DP Marais hospital. Otherwise, the patient will start their treatment and continue treatment at the clinic.

Management of DR TB
In Khayelitsha, patients diagnosed with Rifampicin resistant TB are started on: Kanamycin, Ethionamide, Moxifloxacin, Terizidone, Pyrazinamide whilst waiting for further DST results. If DST reveals sensitivity to Isoniazid, then INH is added to the treatment regimen; if DST reveals sensitivity to Ofloxacin, then Moxifloxacin is replaced with Ofloxacin in the treatment regimen. (Remember, DST to R and H is reported first, and it takes usually another 6 weeks to get DST to 2nd line drugs).
Pulmonary Conditions

Treatment of MDR TB is usually for 24 months. A minimum of four effective drugs,

preferably five to six are used, tailored to the DST result. There are 2 phases of treatment; the first phase (Intensive Phase) lasts a minimum of 6 months and includes an injectable; the second phase (Continuation Phase) lasts a minimum of 18 months. For XDR, duration/termination of treatment is assessed on a case by case basis. (See Appendix 21 for building a treatment regimen).

The basic principles of treatment are:

Include first-line (E, Z) drugs to which infecting strain is susceptible Include a minimum of four drugs, preferably five to six. Do not rely on drugs to which resistance is suspected (i.e. if a patient was taking Z and failed SCC (smear and culture positive) then the mycobacterium may be resistant to Z (DST is not currently done to Z at NHLS).

Use DOT (directly observed therapy for all doses). This could involve a treatment supporter/buddy. Aggressively treat all side effects. This is very important to prevent patients from defaulting.

EPTB DR TB is treated using the same strategies and duration of time as DR PTB.

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Pulmonary Conditions

Monitoring of DR TB?
Patients on treatment for DR TB need to be monitored carefully. This is crucial to their outcomes. Drugs for resistant TB are hard to take and can cause many minor and life threatening side effects. It is the responsibility of the HCW to be aware of the side effects of these drugs and monitor their patients appropriately. (See Appendix 22 for a step-by-step approach to managing DR TB clients). It is also important to monitor patients for the further development of drug resistance, hence the routine monthly monitoring of sputum with smear and culture (and DST if culture remains positive after 4 months of treatment or becomes positive again after conversion).

Contact Tracing
All household contacts and persons spending many hours a day with the patient in the same indoor space of DR TB patients are at risk for developing DR TB. Asymptomatic adult contacts WHO does not recommend universal use of second-line drugs for preventive therapy in DR TB contacts. Asymptomatic contacts should be advised that they have been exposed to DR TB, advised of the symptoms of TB and, if they develop any TB symptoms, they must go to their clinic and report that they are a DR TB contact. By doing this, they will be investigated for DR TB with smear, culture and DST. Symptomatic adult contacts Symptomatic contacts should be screened for DR TB, with smear, culture and DST Paediatric contacts All paediatric contacts should be evaluated for active TB. This includes: istory of Symptoms: Symptoms of TB in children can be non-specific, e.g. H chronic cough or wheeze, failure to thrive and recurrent fevers. Signs of TB on examination e.g. enlarged lymph node, pleural effusion, ascites, etc Symptomatic paediatric household contacts of DR TB should be referred to the TB doctor and receive: 1. Clinical examination including weight gain, lymphadenopathy, respiratory signs, etc. 2. Tuberculin skin testing (TST) 3. Chest x-ray (AP and Lateral)

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4. Culture and DST: If the child is very young or cannot expectorate sputum, sputum induction or gastric aspiration should be performed. Asymptomatic paediatric contacts < 5 years and HIV infected children of any age are to have a TST and CXR and be referred to the TB doctor.

REMEMBER All MDR/XDR TB/HIV co-infected persons

should be initiated on ARVs after 2 weeks, no matter the CD4 level.

Bacterial pneumonia
The most common causative agents for bacterial pneumonia include Streptococcus pneumoniae and Haemophilus influenza. Staphylococcus aureus and gram negative bacteria are less commonly involved. Pseudomonas aeruginosa (sweet smell) is an opportunistic infection. Pneumonia can happen to anyone regardless of HIV status. But those infected with HIV are more likely to suffer from pneumonia (as well as all other infections found frequently in the general population). Bacterial pneumonia is a rare disease in adults below the age of 40; its occurrence suggests that a person unaware of her/his HIV status might be positive.
Pulmonary Conditions

Clinical presentation
Typically presents more acutely than TB, with: roductive cough, often with yellow or greenish sputum P High temperature Unilateral chest pain Localized crepitations on auscultation

Management
moxicillin 5001000 mg three times daily for 7-10 days or Erythromycin 500 A mg four times daily for 7-10 days (if allergic to Penicillin).

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Pulmonary Conditions

Children
Bacterial pneumonia is very common in young children, and even more so in those HIV infected. A child can die from bacterial pneumonia even after ARVs have been started, so you must be vigilant. Use IMCI guidelines to classify pneumonia into simple or severe. Simple pneumonia Fast breathing without chest indrawing or stridor when calm and without any general danger signs (see severe pneumonia) Treat with Amoxicillin 25 mg/kg/dose three times daily for 7 days Follow up within 2 days of starting antibiotics

REMEMBER Tachypnea (fast breathing) in children is

defined as:
60 breaths or more per minute in children < 2 months 50 or more in children 2-11 months 40 or more in children 12 months-5 years

The respiratory rate should be measured during 1 full minute in young children

Table 10. Amoxicillin dose in children

Given three times a day Weight (kg) Dose (mg) Syrup 125mg/ 5 ml 3.54.9 56.9 710.9 1113.9 1424.9 2534.9 35 125 175 250 375 500 750 1000 5 ml 7 ml 10 ml 15 ml 20 ml Syrup 250mg/ 5 ml 2.5 ml 3.5 ml 5 ml 7,5 ml 10 ml 2 caps 3 caps 1 caps 12 months 35 mos 617 mos 18 mos2 yrs 36 yrs 710 yrs 11 yrs Capsule: 250mg Age

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Severe pneumonia f a child presents with chest indrawing or stridor when calm or any general I danger sign (breathing 60 breaths per minute in a child less than 2 months, difficulty feeding, convulsions, lethargy, or central cyanosis) he must be referred urgently to the hospital. Prior to hospital referral, give the child a first dose of IM Ceftriaxone (75 mg/kg OD). Administer oxygen at 1 L/min and check for hypoglycemia. 3-5 kg: Ceftriaxone 250 mg ( 1ml) 6-9 kg: 500 mg (2 ml) 10-14 kg: 750 mg (3 ml) 15-25 kg: 1 g ( 2 ml in each thigh) If Ceftriaxone is unavailable, give Penicillin G IV 50 000 units/kg/dose 6 hourly for 2 days minimum, followed by an oral antibiotic. This needs to be prescribed by a doctor and the first dose monitored closely in case the patient has an allergic reaction. For HIV exposed or infected children < 1 year, initiate therapy with high-dose CTX in addition to the treatment described above, since PCP cannot be excluded (and is rapidly fatal if untreated). Continue for 21 days. Severely immunodepressed children over 1 year who are not on CTX prophylaxis should also be treated for PCP and bacterial pneumonia. Total intravenous and oral therapy for treatment of severe bacterial pneumonia is typically 10-14 days.
Pulmonary Conditions

Pneumocystis jiroveci Pneumonia (PCP)

An opportunistic lung infection caused by the organism Pneumocystis jiroveci. Think of PCP if the chief complaint is progressive shortness of breath rather than coughing. The HIV client with CD4 200 is at risk.

Clinical presentation
yspnoea (shortness of breath) caused by hypoxemia (low oxygen) is the D main symptom. Initially this occurs only on exertion, but later also at rest. The patient can progress to severe dyspnoea quite quickly. Tachypnoea (fast breathing) Nasal flaring Non-productive or dry cough which is chronic over several weeks Fever is not always present, but when present can be very high. Chest X-ray is often non-specific (but may show ground-glass infiltrate).

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Pulmonary Conditions

Management
If not very hypoxic or dyspnoeic, and strong clinical presumption: igh-dose cotrimoxazole (CTX): dose based on weight: 100 + 20 mg/kg per H day in divided doses; typical dose is 4 single-strength tablets every 8 hours for 21 days (adult > 56 kg). In patients with an allergy to CTX, Dapsone 100 mg/day + trimethoprim 300 mg/day may be used. Add Prednisone 80 mg/day for 5 days, then 40 mg/day for 5 days, and then taper until discontinued. Give Folic acid 5 mg daily whenever a person is taking high-dose cotrimoxazole since CTX depletes the body of folic acid. Anticipate CTX-associated rash which is very common. In case of rash, refer! See the patient at least twice per week.

If severely hypoxic/dyspnoeic or if not responding: efer immediately to hospital since there is a risk of respiratory failure. R After three weeks of treatment with high-dose cotrimoxazole, dont forget to continue giving a preventive dose of cotrimoxazole (960mg i.e. 2 singlestrength tablets), or the PCP can recur. See Table 2 on page 21 for further details. An adult or child who has suffered from PCP is in the final clinical stage of HIV infection and must be enrolled for ARVs as soon as possible!

Children
Clinical presentation CP is common in HIV infected children less than 1 year P In older children, it is seen mainly in severely immune-compromised children not on prophylaxis. Present with: Tachypnoea (50 or more breaths per minute in infants 2-11 months, 40 or more in children 12 months to 5 years) Dyspnoea, severe difficulty in breathing Cyanosis Sudden onset of fever (not always present); may be apyrexial (without fever) or have low grade temperature.

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Chest auscultation is less specific and important compared to the degree of respiratory distress. On chest x-ray one might see a diffuse interstitial infiltrate. PCP is frequently seen in children who are not taking cotrimoxazole prophylaxis, but being on cotrimoxazole prophylaxis does not exclude the diagnosis, especially in an infant, or a child with low CD4.

Management efer for inpatient management R Cotrimoxazole 100 + 20 mg/kg/day given three or four times a day for 21 days. Give first dose prior to referral. In hospital, administer CTX intravenously four times a day. In the ambulatory setting, CTX can be administered orally three times daily if this makes adherence easier for the caretaker. Treatment with cotrimoxazole can be given in addition to the usual treatment for pneumonia (i.e. amoxicillin). In severe cases: add prednisolone 1mg/kg/dose twice daily for 5 days, then 1 mg/kg/dose once daily for 5 days, then 0.5 mg/kg/dose once daily for 5 days Cotrimoxazole prophylaxis after completion of treatment (see Table 17 on page 156) If the child is allergic to cotrimoxazole, dapsone 2 mg/kg/day can be given for partial prophylaxis.
Pulmonary Conditions

Table 11: High dose CTX (for PCP treatment only)

Dose given 4 times a day Weight (kg) Syrup (200 + 40 mg/5 ml) Less than 5 5-9,9 10-14,9 15-21,9 > 22 2,5 ml 5 ml 7,5 ml 10 ml 15 ml 1 tab 1 tab 480 mg tab Dose given 3 times a day Syrup (200 + 40 mg/5 ml) 4 ml 7 ml 10 ml 15 ml 1 tab 1 tab 2 tabs 480 mg tab

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Pulmonary Conditions

REFER
PCP is often fatal unless treated early. It is preventable with cotrimoxazole. Remember to start the HIV exposed infant on cotrimoxazole starting at 4-6 weeks of age, since PCP often occurs early! Must keep a high index of suspicion and initiate immediate treatment along with usual treatment for pneumonia and refer for in hospital management. Enrol for ARVs!

Lymphoid interstitial pneumonia (LIP)

LIP is not an opportunistic infection; it is a chronic condition of the lungs of unknown cause that occurs in HIV infected children. It indicates stage 3 disease. Clinical presentation t is often asymptomatic but at times presents with symptoms I It is important to recognize this condition because the clinical picture (chronic cough) and chest X-ray (miliary appearance) can easily be mistaken for TB. Signs to look for in a child with LIP are: enlargement of the parotid glands and clubbing of the digits. Remember: A child can have both TB and LIP! So making a diagnosis of LIP does not mean that you have excluded the diagnosis of TB! In general, it is helpful to remember that a child with LIP will not be very sick unless he/she has severe progressive LIP (usually this is seen in a child who is not on ARVs). Management IP improves with ARVs. L Specific treatment (including oral steroids) is needed only in severe progressive cases (Oxygen saturation consistently < 92% and/or those developing signs of right sided heart failure). If febrile or acutely symptomatic, give Amoxicillin 25 mg/kg/dose TDS for 10-14 days (to treat bacterial super-infection) If remains symptomatic after multiple courses of antibiotics, rule out TB, then consider prolonged course with oral steroids: prednisolone 1-2 mg/kg/day for 2-6 weeks, then taper. Refer to doctor.

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Pulmonary Kaposi sarcoma (KS)

Pulmonary Kaposi sarcoma is a serious diagnosis with a bad prognosis, even in patients on ARVs.

Clinical presentation
uspect pulmonary KS whenever a patient with cutaneous or oral KS lesions S is having lung symptoms. Pulmonary KS can however occur when cutaneous lesions are absent. Pulmonary KS may imitate TB or PCP. Pleural effusion is common. Chest X-ray is non-specific.

Management
e still have to rule out PTB in patients with cutaneous or oral lesions who W are coughing! Arrange for sputum samples, CXR, and pleural tap if effusion is present. If no TB, refer for bronchoscopy and biopsy if possible. Ideally, these patients require chemotherapy at a referral hospital. At primary health care level, the management consists of symptom relief: Nebulisation with Sodium Chloride (Na Cl) 0.9% solution; Consider analgesics according to severity of pain (see Management of Pain chapter on page 183). Avoid steroid use in those with KS (also avoid steroid use in those with HSV)!
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Notes
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Neurological Conditions
(Brain, spinal cord, and nerve)

Julie Rmy

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Neurological Conditions

Peripheral neuropathy (PN)

Peripheral neuropathy is a frequent problem affecting HIV-positive individuals and it can have many different causes. It can be associated with HIV infection itself. It can also be a result of vitamin deficiencies (Pyridoxine = vitamin B6 ). Peripheral neuropathy can be a side effect of different drugs, including TB drugs (INH) or ARVs (d4T or ddI). Alcohol abuse can also contribute to PN. Drug related neuropathies usually present after the first month of treatment.

Clinical presentation
isturbance of sensation in glove and stocking distribution (hands and feet), D although feet symptoms are most common (especially the soles) Presenting as pins and needles, or a burning sensation Also described as cold feet at night and cramps, mainly in the legs Present in one third of patients with CD4 < 200

Prevention of PN
Try to prevent PN by ensuring that Pyridoxine is always given together with INH If an adult (15 years or older) on D4T needs TB treatment, consider changing D4T to TDF (provided CrCl > 50 ml/min). Do not change to TDF if patient needs streptomycin, treatment for DR TB with amikacin or capreomycin, or if there is any suspicion of virological failure.

General management of PN
Verify symmetrical symptoms. Refer same week to doctor if neuropathy is asymmetrical, associated with other neurological signs or loss of function. If an adult is on D4T and develops symptoms of PN, no matter the severity, change D4T to TDF (provided CrCl > 50). For the child, change D4T to ABC or AZT. If the PN is severe, think about checking the lactate level (since PN can be associated with mitochondrial toxicity). If the patient is on DDI and develops PN, initiate specific treatment and refer to doctor. (Consider replacing AZT+ddI with TDF+3TC) Make sure there is no high alcohol consumption

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Treat according to severity and review after 2 weeks If improvement, continue specific treatment If no improvement and client not on ARVs, reassess clinical stage, and refer for stronger analgesia and assessment for ARVs. HIV neuropathy is common in advanced HIV.

Management if on TB treatment Try to prevent PN by ensuring that Pyridoxine is always given together with INH. Pyridoxine (used to both prevent and treat PN): Start at 50 mg once daily (at night) plus thiamine 100 mg once daily Increase pyridoxine up to 200 mg orally once daily if necessary If improvement: Continue pyridoxine until TB treatment is completed.

If an ARV drug is the culprit, try to change to a new ARV (for example, switch d4T to AZT).

Amitriptyline 25100 mg at night (if PN is moderate-severe). Start with 25 mg at night and increase progressively by 25 mg up to max 100 mg if necessary.

Always associate amitriptyline with analgesics Analgesics: Paracetamol 5001000 mg four times daily as required, or, Ibuprofen 200400 mg three times daily as required, or Paracetamol + codeine 1-2 tablets four times daily as required (only if PN is moderate-severe)
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Children
N is less common in children than in adults but to diagnose peripheral P neuropathy (PN) in children is not an easy task. The child sometimes complains of pain in the legs, or refuses to walk. The child needs to be referred to a doctor, who will assess motor function against milestones. This would give an indication if the child has PN. Prevention of PN in a child on TB treatment Pyridoxine: < 5 years 12.5 mg OD; > 5 years 25 mg OD

Dosages for treatment: Pyridoxine: < 5 years: 25 mg/day; > 5 years: 50 mg/day Amitriptyline: 6-12 years: 10 mg 25 mg at bedtime; over 12 years: 25 mg50 mg plus paracetamol 20 mg/kg three to four times/day

If the child is on D4T and is assessed as having PN (no matter the severity), change D4T to ABC.

Bacterial meningitis
A bacterial infection causing acute inflammation of the meninges (or coverings) of the brain and spinal cord (especially Neisseria meningitidis and Streptococcus pneumoniae).

Clinical presentation (also see Algorithm 2 on page 33)

Bacterial meningitis is characterised by the following acute symptoms: igh temperature H Headache not responding to analgesics Vomiting Photophobia Sometimes a decreased level of consciousness

On physical exam, dont miss: Neck stiffness (but not always present!) Kernigs (pain in the lower back when the knee is extended with the patient supine and the thigh flexed at the hip) and Brudzinskis (flexion of the hips when the neck is flexed with the patient supine) signs, and Petechial rash on the body

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Management
A lumbar puncture (LP) must be performed as soon as possible at the hospital and the fluid sent for different investigations. Start empiric treatment with an intravenous antibiotic such as Ceftriaxone 1 g IV. If it is not possible to refer for an LP for whatever reason, do not delay in giving an antibiotic if the person is sick and bacterial meningitis is suspected! While waiting for the ambulance, start empiric treatment with intravenous Ceftriaxone 1g IV ASAP in order to prevent death!

Children
ymptoms are: fever, headache, lethargy/coma, irritability, abnormal cry, poor S feeding and vomiting, stiffness of the neck, convulsions. For small infants: bulging fontanel (although not always present). Children < 2 months: IV ampicillin 50 mg/kg IM/IV QID and gentamycin 7.5 mg/kg IM/IV OD (ampicillin, unlike ceftriaxone, is also active against Listeria monocytogenes). Children > 2 months: ceftriaxone 100 mg/kg/dose IV or IM during 10 days OR treat according to hospital protocol.

Cryptococcal meningitis
Cryptococcal meningitis is less acute in onset than bacterial meningitis: while most common symptoms might be present, they are usually milder. It is caused by Cryptococcus neoformans. It only occurs in AIDS patients with low CD4 counts and places an adult or child into WHO stage 4. It is not contagious.
Neurological conditions

Clinical presentation
rogressive mild headache, often frontal (between the eyes) not responding P to analgesics Neck stiffness might be present Nausea and vomiting Sometimes associated with disorientation, confusion, or seizures Temperature slightly increased Sometimes Cryptococcal skin lesions appear over the body (these lesions can look similar to those of Molluscum contagiosum)

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Neurological Conditions

Diagnosis
he patient must be referred for a lumbar puncture, Indian ink stain and T cryptococcal antigen test (= CLAT = more sensitive) to detect Cryptococcus.

Management
Refer to hospital for amphotericin B IV V Amphotericin B: 0.7 mg/kg/day for 2 weeks, followed by fluconazole 400mg I daily for 8 weeks, and then fluconazole 200mg daily as secondary prophylaxis. If IV Amphotericin B is not available, give Fluconazole 1200mg daily for 1012 weeks followed by Fluconazole 400 mg daily for 10 weeks followed by secondary prevention with Fluconazole (see below). All patients with Cryptococcal disease must be enrolled to start ARVs as soon as possible!

Secondary Prophylaxis
Fluconazole 200 mg daily should be continued in order to prevent Cryptococcal meningitis from coming back. This is referred to as secondary prevention (see page 18). This can be discontinued if the CD4 > 200 cells/l and the person has been on fluconazole for at least 6 months. Fluconazole is teratogenic, so women on prophylaxis should be advised to delay any pregnancy until fluconazole prophylaxis can be safely discontinued.

Children
Refer to hospital for amphotericin B IV IV Amphotericin B: 0.5-1 mg/kg/day for 2 weeks, followed by fluconazole 12-15 mg/kg daily (max 400 mg) for 8 weeks, and then fluconazole 6 mg/kg daily for secondary prophylaxis. Until recently, lifelong secondary prophylaxis was recommended. However, discontinuation should be considered (after being on prophylaxis for at least 6 months) in asymptomatic children aged 6 years or above, on ART with sustained CD4 > 200 cells/l.

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TB meningitis (TBM)
Tuberculosis can infect almost any part of a persons body. When it involves the brain and spinal cord, a person is suffering from tuberculous meningitis (TBM).

Clinical presentation
rogressive onset (> 5 days usually) with less acute presentation than that of P bacterial meningitis Headache Other signs of disseminated TB or IRIS (if on ARVs) High temperature

Diagnosis
eferral for lumbar puncture is necessary, looking at biochemical markers (high R protein and low glucose). Confirmed by acid fast bacilli stain and TB culture though this is often negative.

Management
s for PTB treatment: follow the TB Program guidelines. A If severe, dexamethasone 0,4 mg/kg/day is given to reduce intra-cranial pressure

Cerebral toxoplasmosis
Cerebral toxoplasmosis is caused by the reactivation of Toxoplasma gondii cysts, which lie dormant in the brain (following a mild primary infection occurring earlier in the persons life).
Neurological conditions

Clinical presentation
eadache, and sometimes fever H Focal signs such as: Hemiplegia (one-sided paralysis) Hemiparesis (one-sided weakness) Ataxia and difficulty walking

Commonly associated with new-onset seizures Encephalitis-like symptoms such as decreased levels of consciousness and confusion (less frequent).

Management
Seek doctors advice. If not available, refer to hospital for lumbar puncture and CT scan. Because treatment is with oral medication, once the diagnosis is confirmed, the person can be treated at primary care level (unless unstable). If there is no

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Neurological Conditions

improvement after 2-3 weeks, a follow-up CT scan should be arranged if possible (to rule out other problems such as a Tuberculoma or Lymphoma). All patients with Cerebral Toxoplasmosis must be enrolled to start ARVs! Specific Treatment For suspected Cerebral Toxoplasmosis, treat with: igh-dose cotrimoxazole: 4 single strength tablets twice daily for 4 weeks, H followed by two tablets twice daily for 4-8 weeks. Add folic acid 5 mg daily, since high-dose cotrimoxazole quickly depletes folic acid levels. Secondary prevention Continue with usual 2 tablets daily cotrimoxazole prophylaxis until Cd4 count > 200 cells/l for 2 consecutive measures. Children efer to doctor R High dose cotrimoxazole 40 +8 mg/kg/dose three times a day during 6 weeks, followed by usual (secondary) prophylaxis with cotrimoxazole.

HIV encephalopathy/dementia
About 10% of HIV positive patients will develop dementia in the late stages of the disease (CD4 < 200). HAART has decreased the risk of dementia. It is a stage 4 (AIDS) diagnosis.

Clinical presentation
Patients will present with: rogressive memory loss, low mood and their families may report strange P behaviour. They may have abnormal walking pattern and poor balance. Incontinence may also develop. It is very important to exclude any infectious cause (CMV or toxoplasmosis). This is a diagnosis of exclusion.

Management
efer patient to hospital for a Lumbar Puncture/ CT scan R If these are normal, start HAART. Refer same week for ARVs. Response to ARVs is often good. Supportive measures for both patient and family

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Children
HIV encephalopathy has a different natural history in children. It is in an important condition to recognize in children because early ARV initiation can significantly diminish the long-term negative consequences that the child will suffer. Clinical presentation Suspect if: The childs head circumference (HC) is not growing, or If the child has lost milestones that he/she had previously acquired. (For example, a child who was able to sit upright and now is unable to).

REMEMBER This is another reason why it is so important

to measure, record, and plot on a graph the HC of every child < 3 years of age, and to assess developmental milestones of all children. Dont forget to ask the caretaker how the child is developing. She/he usually knows best.
Management If suspected, refer to doctor for confirmation and ARV initiation. For the child with HIV encephalopathy, a multidisciplinary approach works best (including clinical management, psycho-social support and physiotherapy where feasible).
Neurological conditions

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Neurological Conditions

Notes
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Psychiatric Conditions

Francesco Zizola

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Psychiatric Conditions

Mental health problems such as depression, anxiety, psychosis, delirium and substance abuse are more common in PLWHA.

Depression
Depression is very common and under-diagnosed in people living with HIV. It can contribute to weight loss, poor adherence, and those being lost to follow-up.

Clinical presentation
Depression is characterised by: nsomnia/hypersomnia I Reduced motivation/unkept or failing personal hygiene Reduced appetite Poor concentration, libido (sexual appetite), energy Tearful or agitated Melancholia (a profound sadness) Difficult adherence to their medications Increased alcohol intake Decreased ability to function on a day to day basis

Management
Rule out an underlying medical cause for the depression. lucidate potential cause of depression: explore emotional and social issues. E Refer to a support group, social worker and a psychiatrist if necessary. Refer same week to doctor for assessment of need for antidepressant medication. Avoid using Efavirenz Refer for psychiatric assessment if no improvement

Anxiety
Commonly occurs around the time of testing and diagnosing HIV, as well as with advancing disease

Clinical presentation
eeling excessively worried F Agitated Panic attacks Obsessive behaviour

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Compulsive thoughts

Management
rovide psychosocial support: refer for extensive counselling and support P group. Refer for psychiatric assessment if anxiety persists.

Psychosis
Clients with HIV psychosis usually have advanced stage 3 or 4 HIV disease.

Clinical presentation
elusions-fixed false beliefs D Hallucinations e.g. hearing voices Disorganised speech and behaviour Social or occupational dysfunction

Management
If acute psychotic behaviour: refer same day to hospital! Investigation for any underlying cause. Psychotic behaviour can be the manifestation of an underlying opportunistic infection. Exclude fever, focal signs and meningism.

Refer same day for psychiatric assessment

Delirium
This has a high risk of death. Causes include sepsis, hypoxia, alcohol withdrawal, drug toxicity, and hypoglycaemia.
Psychiatric Conditions

Clinical presentation
cute confusion and disorientation A Agitated and aggressive Changing level of consciousness

Management
anage in a calm environment M Check blood glucose level and treat if hypoglycaemic (give thiamine = vitamin B1 orally or by IM injection before starting any glucose infusion, if alcohol withdrawal is suspected) Provide face mask oxygen if client hypoxic Refer same day to hospital

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Psychiatric Conditions

Notes
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Genital and Gynaecological Conditions

Austin Andrews

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Genital and Gynaecological Conditions

Algorithm 9: Syndromic STI Management- Protocols 1&2

Complaint of Urethral discharge or dysuria

Take clinical history and examine: Check for urethral discharge Look for ulcers Check if testicle swollen/tender

Urethral discharge or dysuria without ulcer?

Ulcer present? (in male or female)

Protocol 1

Protocol 2

No Painful or swollen testes? Yes

Painless Ulcer with or without swollen inguinal lymph node?

Painful small blisters?

Treatment for primary syphilis and chancroid 1. Benzathine Penicillin 2.4 MU IM stat, and Refer urgently to a surgeon if testicular torsion twisted testicle is suspected. 2. Erythromycin 500 mg 6 hourly for 7 days 3. If PNC allergic, give erythromycin 500 mg 6 hourly for 14 days 4. Aspirate any fluctuant lymph node 5. Pain relief if indicated 6. Review after 7 days 7. If still present, but improving, repeat treatment 8. If no change, refer to doctor same week

Treatment for gonococcal and chlamydia urethritis 1. Cefixime 400 mg orally stat, or ceftriaxone 250 mg IM stat and, 2. Doxycycline 100 mg 12 hourly daily for 7 days 3. Advise patient to return in 7 days if symptoms persist. 4. If ongoing urethral discharge and possible re-infection or poor adherence, repeat treatment. 5. If ongoing urethral discharge and good adherence and unlikely re-infection, give metronidazole 2 g STAT.

Treatment for Genital HSV

1. Pain relief if necessary 2. Keep lesions clean and dry 3. Acyclovir 400 mg 8 hourly for 7 days 4. Counsel that HSV infection is lifelong and that transmission can occur even if asymptomatic

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Algorithm 10: Syndromic STI Management-Protocols 3&4

Complaint of vaginal discharge without lower abdominal pain? Lower abdominal pain with or without discharge?

Protocol 3 1. Check temperature 2. Examine to confirm lower abdominal pain/tenderness 3. Look for vaginal discharge 4. Do an internal vaginal exam to confirm cervical motion and/or adnexal tenderness 5. Do a speculum exam to see the cervix* (PAP smear if indicated) 6. Exclude pregnancy

Protocol 4

Yes

Thick, white vaginal discharge with itch? Red, inflamed vulva

No

STI suspected? Yes

Recent miscarriage, delivery, or abortion? Pregnant or missed overdue period? Peritonitis (guarding or rigidity on examination? Abnormal vaginal bleeding? Temperature > 38? Abdominal mass? Yes

Treat syndromically for gonorrhea, Chlamydia and trichomonas 1. Cefixime 400 mg orally stat or ceftriaxone 250 mg IM stat, and 2. Doxycycline 100 mg 12 hourly for 7 days (if pregnant or breastfeeding, use amoxicillin 500 mg 8 hourly instead), and 3. Metronidazole 2 g STAT (avoid alcohol for 24 hours; if pregnant, not in 1st trimester) 4. Review in 1 week; pregnant women should definitely be reviewed! 5. If no improvement, refer to doctor Those women with definitely no risk of STI should be treated for vaginitis only: Metronidazole 2 g STAT (avoid alcohol for 24 hours; if pregnant, not in 1st trimester)

1. If dehydrated or shocked: give IV fluids 2. If temp > 38, give Ceftriaxone 1 gram stat and metronidazole 400 mg orally stat 3. Refer to hospital on same day Treat non-severe lower abdominal pain as pelvic inflammatory disease (PID) 1. Ceftriaxone 250 mg IM injection stat. If penicillin allergic give ciprofloxacin 500 mg 12 hourly for 3 days, and 2. Doxycycline 100 mg 12 hourly for 7 days (use amoxicillin 500mg 8 hourly for 7 days instead if lactating) and 3. Metronidazole 400 mg 12 hourly (Avoid alcohol for 48 hours after stopping treatment) for 7 days 4. Review within 2-3 days. If no improvement, refer to doctor

No

Genital and Gynaecological Conditions

Treat as vaginal thrush 1. Clotrimazole vaginal cream applied daily inside vagina (and externally if needed) for 7 days, or 2. Clotrimazole vaginal tab 500 mg stat 3. Avoid washing with soap 4. Advise client to return in 7 days if symptoms persist. 5. If symptoms persist and adherence good, refer to doctor 6. If symptoms persist and adherence poor, repeat treatment. If still no improvement, refer same week to doctor. *If suspicious of cancer, refer the same week.

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Genital and Gynaecological Conditions

Sexually Transmitted Infections (STIs)

(Syndromic management protocols based on WHO flowcharts, Palsa Plus- Primary Care Management, 2008 and MSF Clinical Guidelines, 2004)

General principles
It is very important that STIs be diagnosed and treated in the general population, since STIs are a major cause of HIV transmission. A syndromic approach is used for the management of STIs. This means that treatment is based on signs and symptoms (syndromes), without using diagnostic tests to identify the precise cause of the infection. Syndromic management is costeffective and allows for early treatment of STIs. Since mixed infections are common, syndromic management covers for most possible causes of infection. A good history is an important part of the following four protocols; assess the persons risk factors for STI (age < 21, new partner, or multiple partners) and ask about any symptoms in the partner. A physical examination should always be done to confirm the symptoms. Treatment is then provided at the same visit based on results of the history and physical examination. A follow-up appointment in one week for reassessment should be regularly advised. Partner treatment is essential to avoid pingpong infections and ensure cure. Family planning, contraception needs (both women and men) should be addressed. Ask about last menstrual period and screen for pregnancy if indicated.

REMEMBER Always consider the Six Cs when dealing

with STIs:
Completion of prescribed medication and Contact tracing (of partner) to achieve Cure. Counselling to Change behaviour and encourage Condom use.

Approach to the partner with an STI

ffer RPR/VDRL and HIV testing to all partners. O Partners who are symptomatic must be treated syndromically.

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Table 12. Asymptomatic partner/s of a client with an STI should be treated based on the clients STI diagnosis
Client diagnosis Vaginal discharge syndrome or lower abdominal pain in woman Asymptomatic partner treatment Cefixime* 400mg orally stat or ceftriaxone* 250 mg IM stat and Doxycycline 100 mg 12 hourly for 7 days and metronidazole 2g stat Benzathine penicillin 2.4 MU IM stat and erythromycin 500mg 6 hourly for 7 days Cefixime* 400mg orally stat or ceftriaxone* 250mg IM stat and Doxycycline 100mg 12 hourly for 7 days and metronidazole 2g stat RPR/VDRL positive Benzathine penicillin 2.4 MU IM stat

Genital ulcer syndrome Male urethritis syndrome or scrotal swelling

* If Cefixime and Ceftriaxone not available or concern about allergy use Ciprofloxacin

Resistance of Gonorrhoea against Ciprofloxacin is becoming common. Therefore, Ceftriaxone 250 mg by intramuscular injection (or cefixime

400mg daily if available) is recommended to treat Gonorrhoea in place of Ciprofloxacin. Refer if no improvement.

Genital and Gynaecological Conditions

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Genital and Gynaecological Conditions

Protocol 1 (Males): Urethral discharge or dysuria

Treat syndromically for gonococcal and chlamydia urethritis: A man with an STI usually complains of discharge and sometimes also dysuria (painful urination). Testicular pain may also signify an STI in males; rarely, testicular pain can result from torsion and this must not be missed (see below).

Assessment
onfirm urethral discharge by examination C If an ulcer is present, use Protocol 2 If painful or swollen testis is detected, refer to a surgeon at once if testicular torsion (twisted testicle) is suspected. Testicular torsion is more likely in a boy less than 18 years who is not sexually active, has no history of injury and no discharge on examination.

Management
reat urethral discharge or dysuria with: cefixime 400 orally stat or ceftriaxone T 250mg IM stat and doxycycline 100 mg 12 hourly daily for 7 days. Advise client to return in 7 days if symptoms persist. If ongoing urethral discharge or dysuria, ask if possible reinfection or poor adherence. If yes: repeat treatment: cefixime 400mg orally stat or ceftriaxone 250mg IM stat and doxycycline 100mg 12 hourly for 7 days If No: Give metronidazole 2g stat. (Avoid alcohol for 24 hours)

Refer if not resolved.

Protocol 2 (Males or females): Genital ulcer syndrome (GUS)

The most common causes of genital ulcer are genital HSV, syphilis and chancroid.

Assessment
onfirm ulcer(s) by examination C Establish first if client has been treated for syphilis. If not, treat syndromically for primary syphilis and chancroid: Painless single ulcer with or without swollen inguinal lymph nodes If there are multiple tiny, very painful blisters (that have become ulcers) and a history of recurrence of these blisters, the diagnosis is more likely to be herpes simplex virus-2 (Genital HSV-2).

131

Management
Syndromic treatment for primary syphilis and chancroid In case of a painless single ulcer with or without swollen inguinal lymph nodes: enzathine penicillin 2.4 million units IM injection STAT and B Erythromycin 500 mg 6 hourly for 7 days. If penicillin-allergic give erythromycin 500mg 6-hourly for 14 days Aspirate any fluctuant lymph node Pain relief if indicated Review after 7 days If still present, but improving, repeat treatment: rythromycin 500 mg 6 hourly for 7 days E Aspirate any fluctuant lymph node Pain relief if indicated and review after 7 days.

If no change: refer to doctor same week

Treatment of Genital HSV ain relief if necessary. P Keep lesions clean and dry. Acyclovir 400mg 8 hourly for 7 days Explain that herpes infection is lifelong and that transmission can occur even when asymptomatic. PLWHA having an episode of genital herpes lasting > 1 month are considered to be in clinical stage 4 and therefore are in need of cotrimoxozole prophylaxis and ART.
Genital and Gynaecological Conditions

Protocol 3 (Females): Vaginal discharge syndrome (VDS)

When a woman complains of a vaginal discharge (and/or burning or itching) it is important to distinguish between vaginitis (inflammation of the vagina) and cervicitis (inflammation higher up of the cervix). It is also important to identify if a woman is pregnant, since some medications should not be used in pregnancy.

Assessment
onfirm abnormal discharge by examination C

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Genital and Gynaecological Conditions

Perform internal examination to check for cervical motion tenderness: If lower abdominal or cervical motion tenderness is present, treat for PID (use protocol 4)

Do a speculum examination to see the cervix. Do a Pap smear if indicated (see below): If suspicious of cancer, refer same week. hose women with definitely no risk of STI, treat for vaginitis only: T If vaginal candidiasis (thrush) is suspected as the cause of the vaginitis (thick, white vaginal discharge with itch), give clotrimazole vaginal cream or tablets (see below). Metronidazole 2g stat. (Avoid alcohol in the first 24 hours. If pregnant, not in the first trimester).

Management

oung, sexually active women should be treated syndromically for Y gonorrhoea, chlamydia and trichomonas: efixime 400mg orally stat or ceftriaxone 250mg IM stat and C Doxycycline 100 mg 12 hourly for 7 days (if pregnant or breastfeeding, use amoxicillin 500mg 8 hourly for 7 days instead) and Metronidazole 2g stat (Avoid alcohol for 24 hours. If pregnant, not in 1st trimester).

Pregnant women must definitely be reviewed in one week. If there is no improvement, refer to the doctor.

Protocol 4 (Females): Lower abdominal pain or cervical tenderness

Lower abdominal pain in women can be the result of many different problems. A thorough history and physical examination is necessary to determine the cause, as well as a urine and pregnancy test. Protocol 4 provides syndromic management of pelvic inflammatory disease (PID).

Assessment
heck temperature C Examine to confirm lower abdominal pain/tenderness. Also do an internal vaginal examination to confirm cervical motion and adnexal tenderness Look for vaginal discharge

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Management
Severe PID Refer to hospital on the same day if: atient very ill, cannot walk upright P Temperature > 38.5 degrees Severe abdominal tenderness or pelvic mass Abnormal vaginal bleeding Pregnant or missed or overdue period Recent miscarriage/delivery or abortion Abdominal mass

If dehydrated or shocked: give IV fluids. f temp 38 C, give ceftriaxone 1g IM stat and metronidazole 400mg orally stat. I Low grade PID If none of the above symptoms and signs are present, then the P.I.D. can be considered low-grade and treated with: eftriaxone 250 mg IM injection stat. If penicillin allergic give ciprofloxacin 500 C mg 12 hourly for 3 days, and Doxycycline 100 mg 12 hourly for 7 days (use amoxicillin 500mg 8 hourly for 7 days instead if lactating) and Metronidazole 400 mg 12 hourly (Avoid alcohol for 48 hours after stopping treatment) for 7 days Reassess in 3 days and refer to hospital if not improving!
Genital and Gynaecological Conditions

Vulvo-vaginal candidiasis (also known as vaginal thrush or yeast vaginitis)

Vulvo-vaginal candidiasis is caused by a type of fungus (a yeast called Candida). It can occur in all women regardless of HIV status. It is not an STI. Vaginal thrush is more common in HIV-positive women for two reasons: 1. HIV-positive women have weaker immune systems and are more likely to suffer from infections in general. 2. HIV-positive women are more often on antibiotics to treat or prevent other infections; this disturbs the normal balance of organisms in a womans body and allows the Candida yeast to overgrow.

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Genital and Gynaecological Conditions

Clinical presentation
urning or itching sensation in the vagina B Associated with a white thick discharge The vulva is often inflamed and itchy

Management
There are many possible topical therapies. Any of the following are suitable but depend on what treatments are available in your clinic: lotrimazole vaginal cream applied twice daily inside vagina (and externally if C needed) for 7 days Clotrimazole vaginal tablet 500mg stat, inserted high inside the vagina at night. Avoid washing with soap Advise client to return in 7 days if symptoms persist If recurrences of vaginal thrush are common (usually > 3 episodes) or the vaginal thrush is resistant to topical therapy: ral treatment with Fluconazole 150 mg STAT dose should be effective. O Fluconazole 50 mg daily for 7-10 days is also effective. Or, repeat clotrimazole. Test for diabetes

If ongoing discharge, no thrush: consider Protocol 3 (vaginal discharge syndrome).

Human papilloma virus (HPV) infection (Genital warts)

HPV is a sexually-transmitted virus. HPV can cause genital warts in men or women. It can also lead to Cervical Intraepithelial Neoplasia (CIN) in women, which are changes of the cervix that can progress to cancer of the cervix. The incidence of CIN has increased with the HIV epidemic, resulting in the recommendation of a Pap smear every 12 to 36 months in HIV infected women in order to screen for any cervical problems. If CIN is found early, these cervical problems can be treated before they develop into cancer.

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Clinical presentation
PV can present externally as genital warts (also known as condyloma H acuminata): They start as small papules, which are often not noticed by the patient. Genital warts can grow to become big cauliflower-like tumours! CIN changes of the cervix resulting from HPV infection can only be diagnosed by Pap smear and internal examination with a speculum.

Management
he treatment of external genital warts is not easy: protect surrounding T skin with petroleum jelly and give weekly applications of 20% tincture of podophyllin or podophyllotoxin topical solution (5mg/ml). Do not apply podophyllin solution internally. Wash solution off after 4 hours. Repeat weekly for 4 weeks. Cryotherapy is the preferred treatment if available. Check for syphylis. If the genital wart lesions are too big and/or not responding, or podophyllin not available, the patient must be referred for surgical treatment.

Genital and Gynaecological Conditions

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Genital and Gynaecological Conditions

Table 13. Cervical screening

Approximately 1 in every 41 women develops cervical cancer. After breast cancer, it is the most common form of cancer among South African woman. Papanicolaou (Pap)/cervical smears detect cervical abnormalities which occur before cancer develops. Cervical cancer is caused by certain types of human papilloma virus (HPV). HPV is usually transmitted sexually. Woman who smoke are more likely to have cervical abnormalities. Advise smokers to stop. An asymptomatic HIV negative woman should receive 3 smears in her lifetime from age 30, with a 10-year interval between each smear. An HIV positive woman should receive a Pap smear on diagnosis, regardless of her age. If the result is normal, she needs the next Pap smear in 3 years. All women with genital warts require a Pap smear. In pregnancy, Pap smears can be performed safely up to 20 weeks gestation. The Ayelsbury spatula is the recommended screening device If the client has a vaginal discharge, treat the discharge first and then take a Pap smear at the follow up visit.

Manage according to the Pap smear result Unatisfactory smear: repeat in 3 months. ASC-US: repeat within 1 year. 2 consecutive ASC-US and HIV positive: refer colposcopy 2 consecutive ASC-US and HIV negative: refer colposcopy ASC-H (ASC-US? HSIL) or AGUS refer colposcopy. Suspicious of cancer: Refer: urgent colposcopy. LSIL: repeat after 1 year. 2 consecutive LSIL: refer colposcopy. HSIL: refer for colposcopy. Normal: arrange repeat Pap date according to HIV status.

Inform client of symptoms of cervical cancer (abnormal bleeding, vaginal discharge) and instruct her to return should they occur. ASC-US: atypical squamous cells of undetermined significance; LSIL: Low grade squamous intraepithelial lesions; HSIL: High grade squamous intraepithelial lesions; ASC-H: Atypical cells-cannot exclude HSIL; AGUS: Atypical glandular cells of undetermined signficance.

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Syphilis
A non-specific blood test for syphilis (called a RPR or VDRL) is recommended annually on all patients attending the HIV clinic. Acquired syphilis is a complicated disease in adults with different stages and many different symptoms. Syphilis can also be transmitted from mother to child and is called congenital syphilis in the newborn.

Clinical presentation
The different stages of acquired syphilis (in adults) include: rimary: painless chancre (ulceration) occurring during initial infection; this P often goes unnoticed! Secondary: various rashes on body several months after primary infection, involves palms and soles Latent: asymptomatic stage Tertiary: late stage of infection causing skin, heart, and neurological problems

Management
If Syphilis is suggested by a positive RPR/VDRL result (confirmed by a TPHA test) give: enzathine penicillin 2.4 million units IM weekly once a week for 3 weeks B If allergic to Penicillin: Doxycycline 100 mg twice daily for 14 days, or erythromycin 500 mg four times daily for 14 days Late-stage syphilis will require 30 days of oral treatment with Doxycycline or Erythromycin; refer to doctor if unsure of stage of Syphilis infection. If pregnant and allergic to Penicillin, refer for assessment by the doctor since there is an unacceptable risk of transmission of Syphilis to the newborn when using Erythromycin
Genital and Gynaecological Conditions

Sexual assault
Sexual assault is often underreported. An open and non-judgmental attitude is essential. Clients will probably not bring up a history of sexual violence unless they feel at ease. Be aware of more subtle signals that the person may send: for example, the client may look depressed, or not look at you in the eye when talking, etc. The physical and psychological consequences of sexual assault are reduced through the provision of medical and mental health care.

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Genital and Gynaecological Conditions

Management of sexual assault

Management of sexual assault includes: Taking and documenting history and performing physical examination IV prevention (PEP) if client presents within the first 72 hours and is HIV H negative. Referral to ART treatment centre if patient is HIV positive. Testing for pregnancy and prevention of unwanted pregnancy, including emergency contraception (levonorgestrel 1.5 mg single dose). STI treatment and prevention (including hepatitis B vaccination if unvaccinated and HBsAg negative or unknown). Tetanus vaccination Trauma counselling

HIV Post-exposure Prophylaxis (HIV PEP) (South African protocol) A risk assessment will be done to determine risk profile and prevention with ARVs if the client is HIV negative. A high risk profile rape includes any of the above: here there have been multiple perpetrators W Anal penetration Obvious trauma to the genital areas Female menstruating at time of rape, or with genital ulcerations/sores

For the HIV-negative individual, prophylaxis with ARVs will be given as follows: AZT + 3TC + LPVr 400 mg/100mg twice daily for 4 weeks Alternative regimen: TDF + 3TC (or FTC) + LPVr for 4 weeks For the choice of ARV regimen, theres no longer any distinction between high and low risk exposure. STI prevention (Non pregnant adults and children > 12 years) efixime 400mg stat dose C Metronidazole 2g stat dose Doxycycline 100mg twice a day for 7 days.

STI prevention (Pregnant adults or pregnant adolescents > 12 years) Ceftriaxone 250mg IM stat dose Erythromycin 500mg 4 times a day for 7 days Metronidazole 2g stat dose

139

Children
e aware of legal age of consent for HIV testing and HIV PEP in children. B For children/adolescents > 12 years, manage as above. Children < 12 years preferably need to be managed at a specialized site where there is expertise in dealing with traumatized children and ART in children. ARV prophylaxis (PEP) for children < 12 years AZT 3TC Add lopinavir/ritonavir if significant exposure has occurred (such as anal penetration or obvious trauma to the genital areas). For drug dosages according to weight, refer to Appendix 9 on page 216.

STI prophylaxis dosages (children < 12 years) Ceftriaxone: 125 mg IM STAT Metronidazole: 7.5 mg/kg/dose 8 hourly for 7 days Erythromycin: 10 mg/kg 6 hourly for 7 days (give doxycycline if over 8 years).

Genital and Gynaecological Conditions

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Genital and Gynaecological Conditions

Algorithm 11: Management of Sexual Assault

Patient allegedly sexually assaulted

For ALL patients Document history and perform medical exam Test for pregnancy & prevent unwanted pregnancy (page 138) Counsel, treat and prevent STIs (page 138) Tetanus &, if needed, hepatitis B vaccination Trauma counselling
If assault occurred more than 72 hours ago If assault occurred less than 72 hours ago

No HIV PEP Counsel for HIV testing

If patient refuses testing

Counsel & provide 3 days HIV PEP starter pack (see risk profile page 138) even if client initially refuses HIV testing
If patient accepts testing* If patient still refuses testing after completion of starter pack

Manage as above

HIV test

Baseline HIV, FBC, LFTs

No HIV PEP

If HIV negative

If HIV positive

If HIV negative

Follow up HIV test at 6 & 12 weeks and 6 months

Patient referred for further HIV management

Continue HIV PEP for total of 4 weeks

If patient tests positive for HIV *

Follow-up blood tests 6 & 12 weeks and 6 months

Baseline HIV testing can be done up to 1 week after the assault, provided that the client has been initiated on PEP on time.

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Notes
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Genital and Gynaecological Conditions

Notes
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Pregnancy and Children

Francesco Zizola

144

Pregnancy and Children

Algorithm 12: Management of HIV positive pregnant women

All HIV-positive pregnant women need: CD4 and clinical staging Folic acid daily in the 1st trimester Multivitamin daily CTX for stages 2, 3 or 4, or CD4 < 200 Screening for TB, and INH prophylaxis if active TB is excluded and not eligible for ARVs. Screening for syphilis and other STIs Ferrous sulfphate (iron) if Hb < 11.0 Usual antenatal care For PMTCT4,5, mother gets: AZT6 300 mg twice daily from 14 weeks At the onset of labour, a single dose of NVP and AZT 300 mg 3 hourly until delivery Then, for tail protection after delivery, a single dose of co-formulated TDF 300mg + FTC 200 mg (1 tablet), or TDF 300 mg/3TC 300 mg

Stage 3 or 4 or CD4 < 350

Stages 1 or 2 and CD4 > 350

Treatment of MOTHER with ARVs: TDF1 + 3TC/FTC + NVP is usual, except if: CrCl < 50 (Use AZT instead of TDF if Hb > 8 g/dl. Otherwise, use D4T) Baseline CD4 > 250 2 On concomitant TB treatment 2, 3 If TB develops while on a ART regimen containing LPV/r, double the dose of LPV/r Start ARVs within 2 weeks, unless TB treatment was also started3

After delivery, BABY gets: NVP at birth7 then daily for 6 weeks. If breastfeeding, NVP is continued for the duration of breastfeeding (until 1 week after). Give NVP 1.5 ml if birth weight (BW) 2.5 kg or NVP 1 ml if BW < 2.5 kg. For dosing after 6 weeks of age, see Table 14 on page 148. Exclusive feeding (breastfeeding or formula feeding) should be promoted during the 1st 6 months of life.
emergency C-section, ensure that the woman receives sdNVP + TDF + FTC/3TC prior to the procedure. 6. Start AZT unless Hb < 8 g/dl or woman is clinically pale. In this case, look carefully for OIs, give iron and refer to doctor. The woman may be eligible for ARVs if no other cause for the anemia is found and the anemia persists despite treatment with iron. 7. If the baby vomits within 1 hour of initial dose, repeat prophylaxis and make sure he doesnt vomit again (observe for at least 1 hour before discharge). If the baby presents for the first time within 72 hours of delivery then NVP should still be given ASAP to the baby and daily for 6 weeks or for the duration of breastfeeding. For late presenters after 72 hours, see Appendix 26.

After delivery, BABY gets: NVP at birth7 then daily for 6 weeks Give NVP 1.5 ml if birth weight (BW) 2.5 kg or NVP 1 ml if BW < 2.5 kg. Exclusive feeding (breastfeeding or formula feeding) should be promoted during the 1st 6 months of life Mother to continue on ART life-long
1. TDF is no longer contra-indicated in the 1st trimester provided that CrCl > 50

2. See first line regimen and pregnancy in Appendix 7 on page 208 3. In case of treatment for TB, wait 2-4 weeks on TB treatment to start ARVs with LPV/r (2 weeks if CD4 < 50). See Appendix 7 on page 210 for progressive doubling of LPV/r. However, if the CD4 count is higher and patient is otherwise stable, try to wait until the end of the 1st trimester before starting ART and initiate with EFV. 4. The following PMTCT regimen can be given even if the woman presents for the first time during labour. 5. For planned (elective) Caesarien section, ARV prophylaxis (sdNVP + TDF + FTC/3TC) should ideally be given 4 hours prior to the procedure. For an

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HIV in pregnancy (including PMTCT)

HIV poses some major challenges to the clinician managing pregnant women. Not only do we want the mother to have a healthy pregnancy, but we also want to prevent the baby from becoming infected with HIV before, during, or after delivery. Different interventions are recommended depending on the womans CD4 count. Note that there is a difference between treatment and prevention with ARVs.

Diagnosis of HIV in Pregnant Women

esting should be done at any ANC visit along with the other usual tests. If T testing is refused, individual counselling should be performed, and HIV testing offered at every visit until status is known. Testing should be done during labour for all pregnant women with unknown status, or immediately after delivery if not possible during labour Testing should be repeated in women who tested negative earlier in pregnancy (every 3 months during pregnancy and the breastfeeding period). Partners should be encouraged to test at every visit

Management of HIV positive pregnant women

Treatment versus Prevention If a pregnant woman has a CD4 count < 350 or is in stage 3 or 4, then 3 ARVs are given to the mother (HAART, or triple therapy) to treat her. Whilst being used for maternal health, this regimen will also help reduce the risk of motherto-child transmission of HIV by reducing the womans viral load. This risk can be further reduced if the newborn receives NVP syrup daily for 6 weeks after delivery. f a pregnant woman has a high CD4 count then ARVs are given to the mother I and newborn to prevent mother-to-child transmission (PMTCT) of the virus. ARVs given to the mother will help reduce her viral load and lower the chances of transmitting the virus to the infant. Women who seroconvert during pregnancy should be put immediately onto AZT prophylaxis, no matter the CD4. If eligible for ARVs, they should then be started on triple therapy within 2 weeks (fast track). HIV can also be transmitted from mother-to-child in breast milk. The risk of transmission in this manner can be reduced if: The mother opts for exclusive formula feeding (no risk of HIV transmission through formula milk), BUT must be affordable, feasible, accessible, safe and sustainable (AFASS) or,
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Pregnancy and Children

The mother opts to exclusively breastfeed for 6 months (decreased risk of transmission compared to mixed feeding), and NVP prophylaxis is continued throughout the breastfeeding period (unless mother is already on lifelong ART).

It is very important that infant feeding options be discussed with the pregnant women during her pregnancy (see infant feeding section page 157159).

ARV treatment, the risk of MTCT through breastmilk is minimal, so for mothers not on lifelong ART, eligibility for ARVs should be reassessed regularly (and CD4 repeated at 6 weeks post-partum then every 3 months).
Monitoring on ARVs Toxicity monitoring for the pregnant woman on AZT is essential Monitor carefully for signs of liver toxicity on NVP. Check ALT in case of symptoms (jaundice, abdominal pain, unusual fatigue, or fever) and in all cases of rash. If on ART, check viral load at least once during pregnancy (after a minimum 2 months of ARVs) Management of the HIV-positive mother post delivery Support the mothers feeding choice. Discourage mixed feeding during the first 6 months of life. Arrange for ongoing HIV care for the mother: Client must not interrupt ARVs and cotrimoxazole prophylaxis. All HIV-positive mothers who received AZT prophylaxis should be reassessed for ARV eligibility (by staging and CD4 in the postpartum period at 6 weeks visit) Discuss family planning. Encourage dual contraception. Discuss care of HIV exposed baby. Remember to write on the infants Road to Health card if ARVs have been received by the mother and infant and what feeding choice has been made.

REMEMBER For breastfeeding mothers on effective

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Care of the HIV-exposed baby

Routine care According to the S.A. National Guidelines, every infant born to an HIV-positive mother should receive NVP (according to weight) for at least 6 weeks. NVP prophylaxis can be stopped at 6 weeks if the infant is exclusively formula fed or if the mother is on lifelong ART. Otherwise, NVP prophylaxis for the infant should be continued throughout the breastfeeding period (and until 1 week after complete breastfeeding cessation). When NVP prophylaxis is continued beyond 6 weeks, NVP dose must be adjusted according to weight and age (see Table 14 for NVP infant dosing). For late PMTCT presenters (after 72 hours) who are breastfeeding see specific management in Appendix 26. First post-natal visit should occur within 3 days, weekly during the first month, then monthly until 12 months, and 3-monthly until 2 years; more frequent visits are indicated if infant is ill. Weight checks and immunisations as per standard schedule (at 6, 10, 14 weeks and at 9 months and 18 months of age according the SA EPI schedule). Give cotrimoxazole prophylaxis to all HIV exposed babies from 6 weeks, daily according to weight (see Table 17 on page 156). This is absolutely essential to prevent early deaths from PCP. CTX prophylaxis continues until the baby has a negative HIV test at least 6 weeks after complete breastfeeding cessation AND does not have any clinical signs of HIV infection (see Table 2 on page 21 for indications). Give multi-vitamins containing vitamin A until HIV infection is excluded or if unavailable, give mega-dose vitamin A as follows: Age of HIV-exposed Dosage of or infected child 612 months > 12 months Vitamin A 100 000 IU 200 000 IU A single dose between 6 and 11 months of age A single dose at 12 months, then every 6 months until the age of 5 years
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Schedule

Test for HIV as seen in Algorithm 13 on page 151; PCR at 6 weeks of age, followed if positive by a viral load test. Counsel about exclusive feeding (breastfeeding or formula feeding) until 6 months of age. See infant feeding section pages 157159 for feeding recommendations during and after the 1st 6 months of life and Appendix 18 (for safe formula preparation)

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If the mother refuses any ARV prophylaxis for the HIV-exposed infant Counselor must intervene to explain the risks of MTCT of HIV and the benefits of prophylaxis. If the mother continues to refuse, consult the head of the facility, and with his/ her permission, provide the necessary treatment in the best interest of the infant (Childrens Act, No 38 of 2005).

Table14: NVP Infant Dosing Guide

Drug NVP syrup (10 mg/ml) Birth Weight or Age Birth to 6 weeks < 2,5 kg birth weight Birth to 6 weeks 2,5 kg birth weight 6 weeks to 6 months 6 months to 9 months 9 months to end of breastfeeding Note: Premature babies need reduced dosing. 20 mg/day 30 mg/day 40 mg/day 2 ml 3 ml 4 ml 15 mg/day 1,5 ml Dose 10 mg/day Quantity 1 ml

Care of the baby when maternal status is unknown (including abandoned babies)
Abandoned babies: If judged to be born since less than 72 hours (and the mothers status is unknown), do a HIV rapid test as soon as possible and If rapid test positive, initiate NVP syrup If rapid test negative, do not give NVP syrup, but schedule the baby for a PCR at 6 weeks anyway. The above management also applies to other cases in which the maternal status is unknown, including cases in which the mother is indisposed due to severe illness, coma, mental illness or death.

HIV in children
With a little practice you will find that caring for children with HIV is not so difficult, even if they are not simply little adults. As they grow, childrens emotional, intellectual and social needs change. Importantly, doses of medications must be constantly adjusted to the childs weight. Remember to communicate with children the way you would communicate with them in your home. Making

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children feel at ease is essential. Simple gestures count, like calling the child by his name, asking her about a favorite hobby or a best friend, and involving him in the discussion (not only the caretaker). For adolescents (roughly ages 10-19, but definitions vary), peer support becomes increasingly important. If available, adolescents are best managed in specialized clinics attached to paediatric clinics.

Definitions
HIV-exposed All children born to HIV infected mothers, when the childs status is not yet confirmed. Diagnostic tests are needed to determine the HIV status. HIV-infected A definitive test has been done to confirm HIV infection. A positive HIV DNA PCR (which detects viral DNA) is diagnostic in infants and children under the age of 18 months. However it still needs confirmation; in SA this is done by means of a Viral Load (which is confirmatory if > 10,000), but this result is not necessary for initiating ARVs. For children above 18 months of age, 2 positive rapid HIV tests (which detect antibodies) confirm HIV infection. Before 18 months of age, it is not possible to know for sure if the antibodies present in the childs blood are the childs or the mothers.

breastfeeding can be reduced if the HIV-positive mother is on lifelong ART, or if the baby receives NVP prophylaxis throughout the breastfeeding period. These children require an age-appropriate HIV test following cessation of breastfeeding after the window period (see Algorithm 13 on page 151).

REMEMBER The risk of HIV transmission through

Pregnancy and Children

How do children acquire HIV?

More than 90% of HIV infection in children is acquired through mother to child transmission during pregnancy, labour and delivery, and after childbirth through breastfeeding. This is why we need to implement effective PMTCT! Other ways children can become infected are: through transfusion with contaminated blood,

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Pregnancy and Children

sexual abuse, or injury with contaminated sharp objects such as razors or needles. As children become adolescents, risk factors are the same as for adults.

Disease progression
Infants and children have an immature immune system and are thus less able to suppress HIV viral replication once infected. Hence, HIV disease can progress much more rapidly in infants and children than it does in adults. This is particularly true for infants less than 12 months of age. If untreated, approximately 40% of HIVinfected children will be dead by their first birthday, and 50% will be dead by age 2.

and children BEFORE they get sick. Since confirmation of HIV diagnosis is commonly delayed in those < 18 months of age, ALL HIV-exposed babies should receive certain interventions (see Algorithm 13). Which children should be tested for HIV?
Unfortunately, HIV diagnosis in children is often delayed. Frequently, we simply do not think about testing the child! It is important to look out for signs and symptoms that suggest HIV infection; if an infant is not growing and developing well (failing to thrive) and/or has frequent diarrhoea or lung infections, the infant is probably HIV-positive. When the PCR result is delayed and if the infant has signs of HIV infection, do not wait for the PCR result: Send the child immediately to an ARV treatment centre!

REMEMBER The goal is to manage HIV-infected infants

REMEMBER Remember to initiate counselling and

testing for HIV AT LEAST for:
All HIV exposed children (Algorithm 13) Children with HIV positive parents or siblings Children diagnosed with TB, severe pneumonia or severe malnutrition Orphans, abandoned children, and children in whom maternal status is unknown ( see management on page 148) Children with signs and symptoms of HIV infection (IMCI classification) Children who have experienced or been at risk of sexual assault (see pages 137139)

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Algorithm 13: Management of HIV-exposed babies

All babies1 born to an HIV-positive mother Start NVP prophylaxis to all newborns for at least 6 weeks If late presenter (> 72 hours after delivery), see Appendix 26

At 6 weeks (integrated with immunization visit if possible): Start prophylaxis with cotrimoxazole (CTX) Perform PCR testing Continue NVP prophylaxis only for breastfeeding babies whose mothers are not on lifelong ART Safe infant feeding counseling and support PCR negative If breastfed (BF): Baby is still at risk Continue CTX until BF stopped and infant confirmed HIV neg If mother not on lifelong ART, continue NVP prophylaxis until 1 week after BF stops Repeat age-appropriate3 HIV test 6 weeks4 after complete cessation of breast-feeding And rapid HIV test at 18 months5 If exclusively formula fed: Baby is HIV negative but still needs to have rapid HIV test at 18 months of age5 Stop CTX prophylaxis if no clinical signs of HIV infection Age-appropriate3 HIV test is negative Baby is HIV-negative Stop CTX prophylaxis and continue routine under 5 care PCR positive2 Baby is HIV-infected: If being fast-tracked, initiate ARVs without delay (see Appendix 4) Ageappropriate3 HIV test is positive Do a confirmatory VL Continue cotrimoxazole If still breastfed and on NVP, the NVP should now be stopped Continue breast-feeding until 2 years of life Ensure well-baby care, including immunizations Give multivitamin daily (or a mega-dose of vitamin A every 6 months) Prescribe de-worming medication every 6 months Clinical staging and developmental assessment every 3 months, with ART referral if eligible (Appendix 4) Do a rapid HIV test after 18 months5 even if prior PCR result was positive
2. All positive PCR results have to be confirmed by second virologic test, but the result shouldnt slow the process of ARV initiation if the child is eligible. In South Africa, confirmation is done by means of a viral load which is confirmatory if > 10,000 copies/ mL. (If VL is <10,000, another confirmatory test will be needed). 3. Age-appropriate HIV testing = PCR in those 18 months, and antibody tests (ELISA or rapid HIV testing) in those > 18 months. 4. Consider waiting until 3 months after complete cessation of breast-feeding if only antibody HIV testing is available. 5. All HIV-exposed infants should have an HIV antibody (rapid) test at 18 months (regardless of prior test results).

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1.

PCR should also be done/repeated in an infant of any age (even if < 6 weeks) if clinical features of HIV infection are present, and results fast-tracked to the clinician. Even if result is negative, a PCR should be repeated at 6 weeks. If PCR is unavailable, but clinical features of HIV are present, do not delay ART initiation: follow WHO criteria for presumptive diagnosis of HIV infection (see Appendix 4).

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Assessment and follow-up of HIV exposed and infected children

Birth history
MTCT regimen use by mother and baby P Mode of delivery (C-section or vaginal) Complications Feeding choice

Interim history
hanges or new illness since last visit C Childs appetite and feeding practices Any new developmental milestones or loss thereof TB and other illnesses in the household New medication and adherence to previously prescribed medications (e.g. cotrimoxazole prophylaxis)

Parental concerns
Note: arents often recognize problems first! p

Social and Psychosocial history

aternal health M Source of income and give advice on how to access childrens social grant Support structures, 2nd care giver Disclosure to child and to others (see Appendix 19 for general guidelines on disclosure to children). Problems with substance abuse, family violence Assess understanding of issues

Tips for the physical Examination

f possible, examine the child in the presence of caregiver I Engage the child (not only the caretaker) Observation is very important Be creative and adaptable; use play when possible Perform potentially uncomfortable procedures last (such as mouth and ear examinations) Children should be undressed for all physical examinations

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Examination
dentify signs of disease progression I Look for physical changes indicating HIV involvement (e.g. enlarged liver or spleen, thrush, lymphadenopathy, dermatitis) Initial examination must be comprehensive and include all organ systems Follow up assessment can be targeted according to history and previous findings Annual complete examination for all children

Growth and nutrition

Growth progression is one of the best indicators of a childs overall health onitor weight, length/height and head circumference M Plot these parameters on growth charts Routine deworming: Age 12 up to 24 months > 24 months Weight < 10 kg Mebendazole 100 mg twice a day for 3 days every 6 months

10 kg or more 500 mg as a single dose every 6 months

Advise parents about safe food preparation (e.g. washing hands, sterilizing teats and other utensils, clean water, preparing one feed at a time etc.). Advise care givers about improving the nutritional value of meals e.g. adding vegetable oil, margarine or peanut butter to the childs porridge, samp, rice or potatoes

If child is failing to thrive, look for treatable causes and manage these appropriately e.g. chronic diarrhoea, TB, malnutrition. Food supplementation where indicated

REMEMBER Stunting in children

Stunting means that children are not growing well in height. A child may appear to be proportional (normal weight for height) but still be stunted (height for

Pregnancy and Children

age < 3rd centile). Chronic malnutrition in the HIV infected child can cause this to
happen. This is another reason why it is so important to measure all the growth parameters of children including weight and height (and head circumference for the child < 3 years) and to evaluate these (by plotting them on curves, e.g. weight for age and weight for height or, height for age).

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Pregnancy and Children

Developmental Assessment
easuring and plotting head circumference can help to identify poor brain M growth Abnormal development should raise concern of disease progression Loss of previously attained milestones could be a sign of HIV encephalopathy: in this case, refer immediately for HAART Ask the care giver about the childs achievements and their concerns

Table 15. Developmental Checklist

1 month 2 months 4 months 6 months 9 months 12 months 18 months Raises head, alert to sound, makes crawling movements Holds head at midline, lifts chest off the table, smiles Rolls front to back, laughs Sits supported, babbles Pulls to stand Walks alone, uses single words Can remove garment, scribble, run

Table 16. Developmental Warning Signs

6 weeks No eye contact, no smile, poor suck, Floppy excessive head lag 6 months 10 months Doesnt reach for object with both hands, no response to sound, poor social response to people Unable to sit unsupported, hand preference, fisting Persistence of primitive reflexes 12 months 18 months Unable to bear weight on legs No walking No single word with meaning

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Dental Evaluation
Dental caries and periodontal disease are common in HIV-infected children of all ages dvise and encourage good oral hygiene A Refer to dentist when indicated

Staging of HIV disease

linical staging every 3-6 months C According to the revised 2007 WHO staging (see Appendix 2) CD4 count evaluation 3monthly for infants, 6monthly for children

Children are born with high CD4 counts. CD4 levels gradually decrease to adult levels by 5-6 years of age. This is why we use CD4 percentages to monitor the younger childrens (below 5 years) immunological status.

The CD4% is a better marker of immune status.

Management of intercurrent medical problems

These include common childhood infections, skin conditions, tuberculosis, etc. They are discussed in prior chapters.

Immunisation
ll children should be immunized according to the national immunisation A schedule and according to the WHO Expanded Program on immunization (EPI). Is of vital importance in preventing and reducing the severity of some conditions in HIV infected infants. BCG vaccination BCG vaccination should routinely be given to newborns at birth except if the mother has pulmonary TB. In this case, INH prophylaxis should be given to the baby, if asymptomatic, for 6 months according to protocol (see page 96). If BCG vaccination is delayed because the mother has TB (see page 96 for specific criteria), the HIV-uninfected, exposed infant may receive vaccination after completion of prophylaxis (provided active TB is excluded). The HIV-infected infant should not receive BCG until on ART and having strong immune recovery. HIV exposed or infected children who receive BCG should be closely followed to provide early identification and treatment of any BCG-related complication.
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Cotrimoxazole Prophylaxis (also see Table 2 on page 21)

If taken regularly, CTX protects against neumonia, especially PCP P rain infections (toxoplasmosis) B ertain types of diarrhea C ther bacterial infections, such as UTI O alaria M

Table 17. Cotrimoxazole prophylaxis dose

Weight (kg) <5 513.9 1429.9 30 Daily preventive dose of Cotrimoxazole dose [given as syrup (240 mg/5 ml) or tablet (single-strength, 480 mg)] 2.5 ml 5 ml or half a tab 10 ml or one tab 2 tabs

Treatment with ARVs

ARV enrolment criteria are detailed in Appendix 4 Follow-up on ART is discussed in the ARV chapter (page 161)

Ongoing education and support of families

Provide ongoing counselling for child and caregiver and refer appropriately for specialized care and social and community based programs. Discuss: ssues with breast feeding I Changes in family structure, illnesses Financial difficulties Disclosure issues (See Appendix 19)

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Infant feeding
General considerations:
ounselling on infant feeding should be started after the first post-test C counselling session during pregnancy and infant feeding should be discussed with women at every antenatal visit. The decision will depend on her preference, social or family support, availability and affordability of formula, and whether she has regular access to safe, clean water. Encourage exclusive feeding during the first 6 months. Discourage mixed feeding as it increases the risk of childhood infections. Before 6 months of age, the infant does not need any food other than milk to grow. After 6 months, complementary foods are necessary for the infants growth and should be introduced even though the breastfeeding mother is encouraged to continue breastfeeding beyond 6 months (together with NVP infant prophylaxis if the mother is not on lifelong ART).

Exclusive breastfeeding during the first 6 months of life means baby gets only breast milk (no formula, tea, water, cereal, traditional medicines),

oral polio vaccine and cotrimoxazole prophylaxis. Medications prescribed at the health centre or hospital to treat inter-current medical problems, are also allowed. Likewise, exclusive formula feeding means baby gets only formula (no breast milk!).

Breast feeding (BF)

The health and child survival benefits of breastfeeding should be emphasized. The risk of transmitting HIV through breast milk is reduced if the mother is on lifelong ART or if infant NVP prophylaxis is given throughout the breastfeeding period (until 1 week after). Encourage exclusive breastfeeding for the first 6 months of life From 6 months of age, introduce nutritious complimentary foods Encourage continued breastfeeding after 6 months of age. Unless the infant is already found to be HIV-positive, it is preferable to stop breastfeeding at 12 months, in order to stop infant NVP. However, if weaning at 12 months would compromise the nutritional status of the child, the mother should be encouraged to continue breastfeeding beyond 12 months (up to 2 years), while the infant continues NVP prophylaxis.
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Pregnancy and Children

If the babys PCR result is positive (confirmed by a VL > 10,000 copies/ml), the mother should be encouraged to continue breastfeeding until at least 2 years. Mothers who are not on lifelong ART and who decide to stop breastfeeding at any time should do so gradually over 1 month whilst the baby continues to receive daily NVP (until 1 week after all breastfeeding has stopped). Abrupt weaning is no longer recommended.

Baby should feed on demand Within 1 hour of delivery ensure correct latching occurs (enough areola in the mouth) to prevent cracked and sore nipples If cracked nipples, mastitis or breast abscess occur, client to stop feeding from the affected breast, express and heat-treat the milk, and cup-feed baby. Mother to check the babys mouth regularly for sores. Assess mothers nutritional status. Check BMI. Refer to dietician. No bottles, teats or pacifiers.

How to heat treat milk to rid it of HIV and bacteria.

Place breast milk feed in sterilized peanut jar. Close lid and place in pot. Fill pot with water 2cm above the level of the milk and heat water. Remove the jar as soon as water is rapidly boiling.

Formula feeding (FF)

ormula feeding is an option if it is affordable, feasible, accessible, safe and F sustainable (AFASS criteria) Ensure client has family support to formula feed exclusively during the first 6 months. Advise client to strap breasts to inhibit milk supply Advise on management of breast engorgement: express milk, apply cold cloths. At each visit ensure client can mix formula properly and is cleaning utensils adequately (See Appendix 18) At 6 months of age, infants with or at risk of poor growth should be referred for continued nutritional monitoring and dietary assistance. Infants weighing < 2 kg should receive a special low birth weight formula (not soy-based) until the infant weighs at least 2 kg.

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REMEMBER If the HIV-positive mother meets AFASS

criteria and opts for exclusive FF, safe practices should be discussed at every visit
Give clear guidance regarding volumes and frequency of feeding needed at each age (see Appendix 18) Discuss dangers associated with bottle-feeding. Discuss and demonstrate cup feeding as a recommended alternative to bottle feeding Discuss home support for avoiding all breastfeeding; ensure that the woman has a carer/supporter outside the health facility to help her avoid all breastfeeding.

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Notes
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Antiretrovirals (ARVs)
Also known as Antiretroviral Therapy (ART) or Highly Active Antiretroviral Therapy (HAART)

Mariella Furrer/THINK pictures

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Antiretrovirals (ARVs)

Perspective
Antiretrovirals (ARVs) have become standard treatment for those people in the late stages of HIV infection with severely weakened immune systems. ARVs do not eradicate HIV, but block its replication, which then allows the immune system to recover some of its strength. Put more simply, ARVs stop HIV from growing. By doing so, opportunistic infections become less frequent and less severe, and the persons clinical condition markedly improves. Patients on ARVs might still transmit HIV, but the transmission risk is much lower.

Principles of Therapy with ARVs:

1. Not all HIV-infected people need ARVs Results of clinical staging and CD4 count testing are used to decide when to start ARVs for adults and older children (see Appendices 7 and 8 ). For infants, the situation is different. Infants are at a very high risk of dying before the age of 2 years, so early treatment with ARVs should be given to all HIV-positive infants under 12 months, regardless of clinical or immunological status. 2. Some HIV-infected people need to be fast-tracked for initiation within 2 weeks
Require fast track (i.e. ART initiation within 2 weeks of being eligible)

Pregnant women eligible for lifelong ART OR Patients with very low CD4 (< 100 cells/L) OR Stage 4, CD4 count not yet available OR MDR/XDR TB Children younger than 1 year

3. ARVs can be given either for treatment (i.e ART) or prevention (PMTCT, Post-exposure prophylaxis, or post-rape). 4. HIV can easily develop resistance to individual ARVs. For treatment purposes, three ARV drugs are given together (Triple therapy) in order to prevent resistance of HIV to individual ARVs. This concept is similar to that seen in TB treatment, where multiple TB drugs are given simultaneously to stop TB (and avoid resistance to TB drugs). 5. We must do everything possible to prevent resistance from developing. Treatment with ARVs is a life-long treatment. ARVs stop HIV from growing only if they are taken faithfully every day. If someone stops ARVs, HIV will start to grow again (and weaken the immune system). ARVs must be taken correctly

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as prescribed (at the right time, the right dose, and every day!). If they are taken irregularly, resistance will develop and the HIV will once again start to replicate in the presence of the three ARVs. Support is needed to enable a person to take ARVs every day. The person (or caregiver, in the case of a child) must live in a stable, supportive environment, must believe in the usefulness of ARVs and must be motivated to take them! She/he should attend a support group for people living with HIV. She/he should have disclosed her/his HIV status to at least one person in whom they trust. Living in denial is a contraindication for ARVs. The development of resistance means that those three ARVs wont be effective ever again for that person, even if they are subsequently taken faithfully. The only chance that person then has to lower the HIV viral load is to start taking three new ARVs (known as second line treatment). It is better for a person to wait and be ready to start ARVs than to take them incorrectly. 6. Change one ARV in case of a severe side effect; change all 3 ARVs if the regimen has failed. Changes may be required for several reasons. Some people may have a major side effect to one ARV. Other times, a whole regimen fails (usually due to earlier problems with adherence). The two main reasons for changing are: Substitution for side effect: Change only the one culprit drug. See Appendix 12 on page 223. Switch for failure: The whole regimen has to be changed because the HIV in that particular persons body has developed resistance to all three ARVs. The three original ARVs are replaced with three new ARVs (a second-line regimen). Changing regimens is a serious decision. The nurse, counsellor and HIV doctor should discuss each case before changing regimens. The first-line regimen is always a persons best chance at maintaining an undetectable viral load; we must help people on first-line ARVs to be faithful to their treatment! Always try to correct a problem with adherence before switching to a second-line regimen. If the HIV in a persons body has developed resistance against the first-line ARVs because of poor adherence, the same will happen against the second-line ARVs unless the adherence problem is corrected! 7. Treat any OIs (especially TB) before starting treatment with ARVs. Thoroughly assess for OIs, other HIV-related conditions (such as anaemia and PN), and contraceptive issues before deciding on the first-line regimen. See
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Antiretrovirals (ARVs)

Appendices 3 and 4. Always try to stabilize the patient as best as possible (by treating TB and other OIs, and improving nutrition) before starting ARVs.

Monitoring on ARVs
Criteria for enrolment for ARVs and 1st and 2nd line regimens in adults are detailed in Appendices 3 and 7. After initiation of ART, patients must be monitored for: possible side effects efficacy (success) of ART and development of resistance Monitoring on ART Clinical stage CD4 at month 6, 1 year on ART and then every 12 months VL at month 6, 1 year on ART and then every 12 months ALT if on NVP and develops rash or symptoms of hepatitis FBC at month 1, 2, 3 and 6 if on AZT Creatinine at month 3 and 6 then every 12 months if on TDF Fasting cholesterol and triglycerides at month 3 if on LPV/r Purpose To monitor response to ART To monitor response to ART To monitor response to ART To identify problems with adherence To identify NVP toxicity To identify AZT toxicity To identify TDF toxicity To identify LPV/r toxicity

2010 S.A. Guideline monitoring recommendations

Monitoring for possible ARV-related side effects

Clinical and laboratory monitoring should be performed frequently in the first few months after ART initiation in order to diagnose and manage any short-term side effects early. See Appendices 10, 11, and 12.

Monitoring for Efficacy (Success) of ART

The measurement of the success of treatment with ARVs can be done in three ways: 1. Clinically (by monitoring for subsequent infections) 2. Immunologically (by monitoring CD4 counts) and 3. Virologically (with viral loads). Clinical monitoring Allow 4-8 weeks on ARVs until the first positive effects are seen: weight gain, improvement in general health, and fewer new infections. After starting ARVs, opportunistic infections can still occur, especially if CD4count < 100. Infections

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can also worsen several weeks after ART initiation, a situation called IRIS (Immune reconstitution inflammatory syndrome). Look for signs of infection, particularly TB, at each visit. Check weight. Investigate weight loss > 1.5kg in 4 weeks. Weight gain > 10kg or a BMI > 28 increases the risk of lactic acidosis. These clients, if on D4T-containing regimens, need substitution of D4T with TDF (provided CrCl > 50) or AZT (if CrCl < 50 and Hb > 8.0 g/dl).

make sure to stabilise your patient before starting ARVs! They slowly stop the HIV from growing and a person gradually feels better. If a person has a very low CD4 count when starting ARVs, that person is still at risk of suffering from serious infections in the first 6 months on treatment. Almost all people who die in the first 6 months on ARVs do so as a result of new serious infections. They do not die from starting ARVs!
CD4 Lymphocytes The white blood cells which are targeted by HIV are called CD4 cells. These CD4 cells help a persons immune system to fight infection. In healthy individuals, there are 500 - 1000 CD4 cells per microlitre of blood. Following infection with HIV, the CD4 cells in a persons body are attacked by the replicating HIV and the CD4 count gradually drops. The speed at which the CD4 count drops is different in different people. The CD4 count will eventually drop down to zero, unless a treatment (ARVs) is started to fight the HIV. The absolute number of CD4 cells determines the risk for development of HIV-associated diseases (see Table 1 on page 3). Treatment with ARVs interrupts the life cycle of HIV, so HIV stops growing and stops killing the CD4 cells. The CD4 count then slowly rises (usually to a level well above 200). However, this can take many months or years, and will only continue if the person is faithfully taking the ARVs. This level of 200 is important, since most OIs occur when the CD4 count is below 200.
Antiretrovirals (ARVs)

REMEMBER Note that ARVs do not work instantly so

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Antiretrovirals (ARVs)

Viral Load Viral Load (VL) < 400 copies/ml 4001000 copies/ml Response 6-monthly viral load monitoring and routine adherence support Assess adherence carefully Repeat viral load at 6 months > 1000 copies/ml Intense adherence assessment Repeat viral load in 3 months; check hepatitis B status, if not done already If < 1000, return to routine 6-monthly monitoring If > 1000 and adherence issues addressed, switch to second line therapy after hepatitis B status checked
2010 S.A. Guideline recommendations for virological monitoring

This blood test measures how much HIV is in a persons blood. It does not measure how the patient is feeling or how high the CD4 count is. After several months of ARVs (usually no more than six), the HIV viral load should fall to undetectable levels. This undetectable level (also known as LDL or lower than detectable limit) is important since it means that the HIV has stopped growing as a result of the ARVs. Where viral loads are available, they are used to monitor a clients progress and make decisions about switching to second line (See Algorithm 14 on page 169). A previously undetectable viral load may rise and become detectable again for the following reasons: he person is not taking the ARVs faithfully. T The person is taking the ARVs incorrectly. The person is taking another medication, which is reducing the effectiveness of the ARVs (this can occur with both TB meds and traditional medicines). The blood sample was mixed up with that of another patient. The person is suffering from an intercurrent illness (TB, common cold, etc), which boosts replication of HIV. We call this a blip in the viral load. Frequent vomiting or diarrhoea, which prevents absorption of ARVs into the body. Remember: Never take blood for a viral load for monitoring purposes in a patient who is feeling sick (not even a common cold).

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Monitoring of children on ART

ARV enrolment criteria and 1st and 2nd line regimens for children are detailed in Appendices 4 and 8. Four main aspects requiring on-going monitoring are: reatment efficacy: clinical, CD4, viral load T Adherence to ART regimen Drug toxicity and adverse events Developmental and psychosocial progress

Treatment efficacy: clinical, CD4, viral load We measure success of ARVs in children the same way as we measure it in adults. In children, we often notice clinical improvement quite rapidly. The child will gain weight and he/she will feel much better. Often the caretaker will be the first one to tell you that the child is now playing, not sick as often, and doing things she/ he wasnt able to do before. Dont forget to weigh the child at every visit and plot the childs weight on a growth curve. This is one of the most sensitive indicators of treatment success! If the child is getting worse in the first months of treatment instead of getting better, you must suspect IRIS: look carefully for any undiagnosed OIs, especially TB. As for adults, the childs CD4% should gradually increase on ARVs and the viral load become undetectable. After 1 year on ARVs, the CD4 % in a severely immunedepressed child < 5 years should have risen significantly above its baseline. For a child > 5 years, you should see an increase of at least 50 cells/l. Criteria for switching to second line treatment in children are discussed later in this chapter. Adherence Adherence poses additional challenges in children for several reasons. Some of these are: the young child is dependent on his/her caretaker to administer the medication at the right time and in the right dosages; fewer fixed dose combinations for children exist; sometimes the child must take syrups which he may not like the taste of, the caretaker can change, etc. Assess adherence at every visit and use every interaction with a caregiver to re-enforce the absolute need for adherence. Also remember that just because a child is adherent today, does not mean that he/she will stay adherent. In particular, as children become adolescents, adherence can become a new challenge.
Antiretrovirals (ARVs)

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Antiretrovirals (ARVs)

Side Effects ART associated side effects occur in children as well as adults. Fortunately they are seen a little less commonly in children. However this means that they may be missed when they do occur. Vigilance and proper education given to the caregiver can help avoid this. For more discussion on side effects and management see section on side effects later in this chapter. Developmental and psychosocial progress How the child is developing can help us decide when the child needs ARVs (see section on HIV encephalopathy page 118). It will also help us see how the ARVs are working. Usually, the caretaker will notice a big improvement in the childs progress once ARVs are started. Also, if adherence is a problem or if the child has developed resistance, we may notice that the child simply is not developing well. This is why it is so important to ask the caretaker how she/he thinks the child is doing. Also clinicians should assess the childs development every 3 months by using the development checklist (page 154).

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Algorithm 14: Viral load (VL) monitoring and switch to

second line
Routine VL measurement at 6, 12 months then yearly in all clients on ARVs

LDL

501000

>1000

Routine adherence support Repeat VL after 6 months, and if still lower than detectable limits (LDL), then yearly Consider referral for nursemanaged care Give increased adherence support Repeat VL in 6 months

Give increased adherence support. Client needs doctor review Repeat VL after 3 months, check HBsAg (in adults)

LDL

50-1000

>1000

>1000

50-1000

LDL

Routine adherence Continue increased adherence support Repeat VL in 6 months Consult doctor Refer to doctor for switch to second line treatment Continue increased adherence support Repeat at 6 months Consult doctor support Repeat VL after 6 months Consider referral for nurse-managed care

Unit for VL result = copies/mL The definition of lower than detectable limits (LDL) can vary, but in the S.A. guidelines this is defined as < 400 copies/mL. Notes: If the client is pregnant, check viral load at least once during pregnancy (after minimum 3 months of ARVs): If > 1000 increase adherence support and repeat viral load after 1 month. If still >1000, client needs referral to HIV specialist. HBsAg should be checked before considering a discontinuation of TDF, since stopping TDF could cause a serious flare of hepatitis (see page 7576).
Antiretrovirals (ARVs)

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Antiretrovirals (ARVs)

Nurse-managed care
The 2010 SA guidelines aim to enable nurses to initiate ARVs for both treatment and prevention, which should greatly improve access to ART. Nurses should be supported by doctors for complicated cases including: omplicated OIs C Serious side effects Complicated adherence issues Children Treatment failure Unstable patients, etc

Second line treatment in adults

ive 2nd line treatment if viral load is raised (as described in Algorithm 14: VL G > 1000 copies/ml two times) with or without opportunistic infections and the client is adherent and getting increased adherence support. Client to get similar work up as before starting 1st line ARV regimen-steps 1-5 (Appendix 3) Second line treatment must be prescribed and monitored monthly by a doctor. Discuss all clients who have received ARVs other than the standard regimen with a specialist. See Appendix 7 for 2nd line regimens and doses of second line drugs in adults Patients failing second line therapy have few treatment options. Failure is almost always due to poor adherence, and every effort should be made to address this, as re-suppression is often possible on the failing drugs.

Criteria for switching to second line treatment in children (South African guidelines)
In South Africa, the same viral load follow-up criteria apply to children and adults, with the only difference being that, in case the child is failing a PI-based regimen, the adherence re-enforcement must be even stronger, and the cut-off for switching is then VL > 5000 copies/mL. Children can get second line treatment if viral load is raised (Algorithm 14) with or without opportunistic infections and the child is adherent and getting increased adherence support. Treatment failure should be suspected in children if there is:

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Confirmed return of CD4 percentage (repeated within 1 month) to baseline (CD4 level before starting ARVs) or below, in the absence of concurrent illness to explain CD4 decline.

More than 50% decline in CD4 % from peak on ARVs (repeated within 1 month) in the absence of concurrent illness to explain CD4 decline.

Lack of growth or decline in growth in a child showing initial response to treatment Loss of neurodevelopmental milestones or development of HIV encephalopathy New evidence of stage 3 or 4 disease after immune reconstitution. (Note: Presentation with TB while on 1st line treatment is not an indication to switch. Also, IRIS is not an indication to switch).

REMEMBER General considerations prior to defining

treatment failure in children:
At least 24 weeks on therapy Always attempt to improve adherence before switching regimens as poor adherence is the commonest cause of virological failure. Treat any intercurrent opportunistic infections Exclude IRIS Ensure adequate nutrition First check adherence: if it is not possible to improve adherence, attempt directly observed therapy (DOT) with a health care worker or another adult living in the same house (see page 202).

Side Effects of ARVs

Important points:
ot every person starting ARVs will suffer from side effects! Only some people N get side effects. Side effects are more common in severely immunocompromised (CD4<200) patients. Side effects can also be classified into those occurring early and those occurring late (see Appendix 11). Side effects can be graded to help differentiate between minor and major problems (See Appendix 12). Instruct the patient to report any side effects early and not to stop any drugs without consulting the nurse or doctor first.
Antiretrovirals (ARVs)

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Antiretrovirals (ARVs)

Algorithm 15: Managing possible ARV side effects

All adults and children started on ARVs

Some people get side effects: perform clinical exam see Appendix 12 for grading of effects (to assess severity) Some people do not get side effects.

A few are major side effects (must be recognised early since they can lead to death if ignored!): Hepatitis (NVP, etc) Pancreatitis (ddI, d4T, etc) High lactate (d4T, ddI, etc) Severe anaemia (AZT) Stevens-Johnson rash (NVP, etc) Hypersensitivity reaction (ABC) Renal failure (TDF)

Many are minor side effects and self-limiting: nausea, dizziness, etc Treat if necessary1 (see Appendices 11 and 12)

Continue to monitor for possible Change culprit drug (or sometimes need to stop all three ARVs temporarily) Notes: 1. Do not change culprit ARV for a minor side effect. Do not systematically prescribe more drugs to treat side effects of ARVs! For example, not all people with nausea need another drug! 2. If someone on ARVs complains of abdominal pain or is losing weight, take blood for relevant tests and refer to doctor ARV side effects at every visit: Check weight Thorough clinical assessment

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Common side effects of ARVs (Appendices 11 and 12)

The following side effects are more common Nausea +/- Vomiting ll drugs can cause this, but it is more common with DDI, AZT, and Protease A Inhibitors (PIs) Nausea already occurs in all HIV patients to some extent. It can become worse when ARVs are initiated, but ARV-related nausea is usually self-limiting (resolves on its own after several weeks on therapy). There is usually no treatment needed. Prochlorperazine or metoclopramide 10 mg three times daily as required may help if the nausea is severe. Change of drug times may help to some extent (for example, DDI can be tried 2 hours after breakfast instead of one hour before breakfast). The more drugs a patient has to take, the more likely there is to be nausea and vomiting (for example, when a person must take ARVs and TB drugs together). If the ARVs are vomited, tell the patient to take the pills again after 2 hours. If the vomiting is very severe or does not stop, then consult the doctor. Take immediate action (refer for immediate assessment) if the vomiting: Is associated with serious symptoms such as fever, severe rash, and/or jaundice (must exclude Hepatitis) Is very severe and does not stop over several days (resulting in dehydration) Is associated with abdominal pain (must exclude Pancreatitis) Occurs in patients who are > 46 months on ARVs (especially D4T and DDI) and is associated with weight loss (must exclude high lactate levels before lactic acidosis develops) Rash ash is a typical side effect of the NNRTI class of ARVs. Most commonly a R concern with NVP; sometimes with Efavirenz. It occurs during the first 4-8 weeks of treatment, and is much more common with Nevirapine (NVP) than Efavirenz (EFV). For this reason, only half of the usual dose of Nevirapine dose is given during the first 2 weeks of treatment. Always recheck the liver blood test (ALT) when you see a rash that might be associated with NVP.
Antiretrovirals (ARVs)

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Antiretrovirals (ARVs)

NVP can be continued in the presence of a mild rash (see below) by an experienced nurse or doctor. However, take immediate action (refer to the doctor for assessment and probably a change of the culprit drug) if the rash: Is associated with serious symptoms such as fever, vomiting, or jaundice (must exclude Hepatitis) Is associated with a significant increase of ALT (> 5 times the upper limit of normal for ALT, which works out to ALT > 200 in an adult) Progresses and becomes very severe (with scaling and skin erosion) Mucous membranes are involved (Stevens-Johnson rash). These patients need to be referred to hospital ASAP!

For a mild rash, Continue the culprit drug (usually NVP), consider extending the lead-in dosing, but see the patient every 2-3 days Chlorpheniramine 4 mg three times daily as required may help reduce itching Topical steroid such as Betamethasone ointment may help (but do not use oral steroids!) If in doubt about what to do, consult the doctor.

Dizziness and light-headedness an occur with Efavirenz, and AZT C No specific action needed. This is why Efavirenz is prescribed at bedtime. If the dizziness does not disappear after a few weeks, EFV may need to be changed to Nevirapine. See Appendix 12 for other possible psychological side effects due to EFV. If there is a concern about anaemia causing the dizziness (sometimes occurring with AZT), check the Haemoglobin and refer to the doctor if the Hb is low on AZT. Peripheral Neuropathy (PN) ccurs most commonly with D4T and DDI O This possible side effect can become serious! Never use D4T and DDI together, since this increases the likelihood of PN. If patient is on D4T and has symptoms of PN substitute the D4T for another drug (usually TDF). This change should be made no matter the severity of the PN. It should be made sooner rather than later as clients may have persistent

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neuropathic pain and/or difficulties walking if left for too long. Always check CrCl if you intend to start TDF. Treat PN as described on pages 112114 and Appendix 12 on page 223 Note that ARV-related PN is probably due to depletion of mitochondrial DNA, the same process involved with a serious side effect called lactic acidosis (see below). Therefore, check the LACTATE level if a patient on D4T or DDI starts complaining of symptoms of Peripheral Neuropathy!

Serious side effects of ARVs

The following possible side effects are potentially fatal if missed or ignored! Hepatitis (inflammation of the liver) epatitis can occur acutely (associated with fever and rash as described above H with NVP) or more chronically (with D4T or Ritonavir). For acute NVP-induced hepatitis, see also Appendix 12 on page 225. Hepatitis is more common when ARVs are used at the same time as TB medication. If the hepatitis is mild, then monitor the ALT regularly to ensure that it is not getting worse. If the ALT result is getting progressively higher, then the culprit ARV must be substituted with a new drug. If you suspect that a patient has severe hepatitis (jaundice and/or abdominal pain), then refer to the doctor immediately. Pancreatitis idanosine (DDI) is the most common cause (D4T and 3TC occasionally) D Pancreatitis can be life-threatening! Think of it and check the serum amylase +/- lipase level whenever someone on ARVs presents with abdominal pain. If in doubt, refer to the doctor; dont send the person home to return in a month! Lactic acidosis (which is preceded by high lactate levels or hyperlactatemia) an occur with any ARV in the NRTI class, but is most commonly due to D4T or C DDI.
Antiretrovirals (ARVs)

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Antiretrovirals (ARVs)

Monitor clinically for hyperlactatemia in all patients taking ARVs for more than 3 months, especially obese people (BMI > 28), pregnant women, those on D4T, and those on DDI.

Watch out for the patient who was stable on ARVs but then starts to feel unwell after 6-9 months (especially when on D4T or DDI). The initial symptoms will be non-specific. If symptoms of high lactate are ignored, then the patient will become sicker and sicker with vomiting, shortness of breath, seizures and even death from lactic acidosis. This is another reason to check the weight on every single visit!

Other clinical features of hyperlactatemia: Fatigue Nausea Vomiting Abdominal pain Loss of weight Shortness of breath

Refer to Algorithm 16 on the next page for the management of suspected hyperlactatemia/lactic acidosis. To help prevent this side effect, D4T is no longer used in usual first line regimens (adults and children), and, for adults, DDI is no longer used in usual second line regimens. For individuals already on regimens containing D4T, this drug should be continued unless side effects develop, or the adult client is at high risk of toxicity (i.e., BMI > 28, TB treatment).

NRTIs cause depletion of mitochondria DNA in the bodys cells (mitochondria = breathing-engines of our bodies cells). This may lead

to impaired cell function and a metabolic syndrome which involves high lactate levels (hyperlactatemia) which can then progress to lactic acidosis. It is very important to identify this side effect early before it progresses to acidosis.

situation of circulatory or respiratory failure (e.g. shock, severe infection, severe pneumonia). All these conditions have to be detected early and managed approriately in order to prevent mortality.

REMEMBER High lactic acid might also be caused by any

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hyperlactatemia/lactic acidosis

Algorithm 16: Management of suspected

Other causes for LOW and abdominal pain may mimic or co-exist with hyperlactatemia/lactic acidosis. Other causes for LOW to consider: OI (ask if TB symptoms) Chronic diarrhoea with malabsorption Virological failure Depression Malignancy Diabetes Lack of food Other causes for abdominal pain to consider: Pancreatitis (check Lipase) Lactate Accutrend measurement and Assess Respiratory Rate Hepatitis/Steatohepatitis (check ALT/ALP) OI or IRIS (e.g. abdominal TB) GI intolerance of meds Unrelated causes (e.g. appendicitis).

Suspected hyperlactatemia/lactic acidosis Unintentional recent loss of weight (LOW) (e.g. > 2 kg in 3 months) Abdominal pain Nausea and vomiting Dyspnoea, tachypnoea without respiratory cause Unexplained tachycardia

Lactate < 2.0

Lactate 2.04.0 And RR < 20

Lactate > 4.0 or Lactate 2.04.0 and RR > 20 without respiratory cause OR

Recheck in 1 week. If remains < 2.0 continue drugs and investigate for alternative causes listed above.

Change D4T to TDF* and recheck Lactate after 3 days then weekly till normalized. If Lactate continues to rise despite change then stop all drugs (with LPV/r for 7-10 days for tail protection) and wait for Lactate to normalize before re-challenge. Seek expert advice regarding rechallenge.

Hyperlactatemia strongly suspected yet Accutrend reading not elevated

Refer to secondary level for formal Lactate measure and Arterial Blood Gas, ALT, ALP, Lipase And, stop ARVs (but consider giving monotherapy with Lpv/r for 7-10 days as tail protection see also page 228)
Antiretrovirals (ARVs)

* If according to the latest VL the patient is failing, or is suspected so for any other reason, better to stop temporarily all ARVs rather than risking a functional monotherapy with TDF (and selecting resistance to it as well).

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Antiretrovirals (ARVs)

Hypersensitivity reaction rare but potentially fatal reaction to Abacavir (ABC) see page 213 for further details

Renal impairment may occur with Tenofovir (TDF) (see page 235) in adults taking TDF, renal function should be routinely monitored by calculating the Creatinine clearance (CrCl)

Other possible late side effects

Lipodystrophy (fat redistribution) an occur with PIs or NRTIs (such as D4T, especially when used in combination C with DDI). Patient will present with increase of fat around abdomen, breast and/or back of neck. Decrease in fat in face, limbs and buttocks. Usually occurs in patients who are on long term therapy. Can be disturbing and stigmatising for the patient. Changing the offending ARV (D4T to TDF) can lead to improvement (but substitution is allowed only if the latest VL is undetectable and adherence isnt a concern). Hyperglycaemia and Diabetes mellitus an occur with Protease inhibitors (PIs). C Consider screening those on LPV/r with regular fasting glucose levels. Management is similar to that of Diabetes. The offending ARV may need to be changed (Eg. LPV/r to ATV/r).

Hyperlipidemia A persons triglyceride and cholesterol levels often rise when taking a Protease Inhibitor (such as LPV/r). If pre-existing severe dyslipidemia and/or high cardiovascular risk (hypertension, diabetes, pre-existing cardiac condition, prior stroke, etc), drug substitution could be considered, from LPV/r to ATV/r or NNRTI (unless resistance to NNTRIs has already occurred or the patient previously suffered from serious NNRTI-related side effects). Screening for hyperlipidemia is recommended at month 3 on LPV/r, then as necessary.

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Immune reconstitution inflammatory syndrome (IRIS):

IRIS is a paradoxical phenomenon that occurs when the patient on ARVs begins to have immune recovery in the setting of an untreated or not fully treated OI. This may lead to a transient worsening of symptoms or clinical status, despite favourable recovery of immunological status (CD4 count/percentage). When this occurs, all efforts must be made to find, diagnose and treat the OI.

Clinical presentation
sually IRIS occurs within the first 2-9 months of initiating HAART (most cases U occur in the first 3 months). IRIS is most common in patients with severe immune-suppression (CD4 < 100) and recent diagnosis of OIs before ART was started. TB, Cryptococcus, Herpes Zoster virus, CMV, NTM, Hepatitis B & C are commonly reported to cause IRIS. IRIS syndrome may present in two forms: 1. The first is the worsening type. This means an OI that was successfully controlled and on continued treatment, worsens a few weeks after start of HAART. 2. The second is the unmasking type. This means a previously undetected sub clinical infection presents with new and frequently unusual manifestations.

REMEMBER The possibility of IRIS should be explained

to patients prior to the initiation of HAART. This will assist with future adherence and help the patient return early for care and management if symptoms do occur. Management
n general, HAART should not be interrupted if the immune reconstitution I syndrome occurs unless a life threatening illness has occurred. Treatment of the unmasked OI is essential, and in severe cases a short course of steroids could be considered: prednisolone 40 mg/day for 2 weeks, followed by prednisolone 20 mg/day for 1 week, followed by 10 mg/day for another week (OI guideline MSF, 2006). It is essential to exclude other diagnoses before prescribing steroids! This should only be done by the doctor.
Antiretrovirals (ARVs)

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Antiretrovirals (ARVs)

REFER
A patient on ARVs needs to be referred to the doctor when presenting with any of the following problems: a severe rash (especially if it involves the mouth and/ or genitals, or is associated with fever, and the patient is feeling sick) severe abdominal pain jaundice loss of weight of more than 2 kg shortness of breath severe vomiting with dehydration severe headache changes in body shape numbness ('pins and needles') in hands and feet that does not improve

Drug interactions
One drug can change the blood or tissue level of another by affecting its absorption, distribution, metabolism (processing in the body) or elimination. Some interactions can result in significant changes in drug levels. This may require the dose of one or more drugs to be changed or to use another drug altogether. See Appendix 13 for some of the most common drug interactions. ic medication

Conclusion
The Comprehensive HIV treatment programs will be most accessible to the general population if they are primary health care-based. Nurses at primary health care level should feel comfortable managing HIV-related conditions and advising about ARVs in adults and children. HIV treatment programs should also be closely linked with TB programs, since the most common cause of death in HIV patients continues to be Tuberculosis. By implementing comprehensive, nurse-based HIV treatment programs across Southern Africa and by using TB Algorithms, nurses will prevent many unnecessary deaths from TB and other opportunistic infections.

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Notes
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Antiretrovirals (ARVs)

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Antiretrovirals (ARVs)

Notes
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Management of Pain

Susan Sandars

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Management of Pain

Figure 5: Pain management (The pain ladder)

Strong opioid 4 (doctor referral) Oral morphine +/- non opioid

If pain persists

Weak opioid (doctor prescribed) Paracetamol + Codeine combination3 +/- non opioid

If pain persists

Non opioid Paracetamol1: 1 gram 8 hourly Ibuprofen2: 400 mg 8 hourly

Start here Notes 1. Refer to Table 18 page 186 for dosage tables of paracetamol for children. 2. This is a non-steroidal anti-inflammatory drug. Do not give if client has a history of gastro-intestinal problems. 3. Refer to Table 19 page 186 for dosage tables of paracetamol and codeine in children 4. Strong and weak opioids should not be combined

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General introduction to pain

Chronic pain and pain syndromes are very common (up to 80% at some point during the disease) in HIV positive patients. If not treated properly they can cause much distress for both the patient and their families.

Definition
Pain is an unpleasant sensory or emotional experience because of tissue or nerve damage. Chronic pain may be caused by a dysfunctional nervous system.

Causes
Common causes of pain in HIV patients: eripheral and sensory neuropathies P Post herpetic neuralgia (after Shingles) Lactic Acidosis Syndromes

Principles of symptomatic management

lways treat the underlying cause A Eg. add pyridoxine 25100 mg daily if patients on TB treatment and ARVs

The World Health Organisation Pain Ladder has been shown to be +/- 90% effective (see previous page and below)

Management Steps of the World Health Organisation Pain Ladder

Step 1
se a Non Opioid Analgesia: Paracetamol 1g 6 hourly U Add non steroidal anti inflammatory drugs (NSAIDS) as required (only if no history of gastrointestinal problems): Ibuprofen 400 mg 8 hourly or diclofenac 50 mg 8 hourly

Step 2
dd a weak Opioid analgesic: codeine phosphate 3060 mg 6 hourly A Paracetamol and codeine (Panado-Co) work better as a combination Add non steroidal anti inflammatory drugs as above

Step 3
Refer to doctor Add a strong Opioid analgesic: Oral Morphine start with 5 mg QID and increase by 510 mg increments as necessary. Injectable morphine may be available in some settings.
Management of Pain

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Management of Pain

Add non steroidal anti inflammatory- as above Do not use a week Opioid and a strong opioid in combination

Management of pain in children

Pain ladder in children Step 1: Paracetamol: 60 mg/kg/day maximum in 3 or 4 divided doses (see Table 18 below) Ibuprofen; Child (> 6 months): 10 mg/kg/day 4 to 6 hourly (max 500 mg/ day) Step 2: Paracetamol + Codeine (see Table 19 below) Step 3: Oral morphine: start with 0.20.4 mg/kg/dose 4 to 6 hourly

Table 18. Paracetamol childrens dose

Paracetamol 125 mg/5ml syrup; 500 mg tablet Weight (kg) 6 to 10 kg 10 to 18 kg 18 to 25 kg 25 to 50 kg Over 50 kg and adult Dose (mg) 60 120 240 500 1000 Syrup (125 mg/5 ml) 2.5 ml 5 ml 10 ml Tab (500 mg) Half a tablet 1 2 Approximate age 3 to 12 months 1 to 5 5 to 8 8 to 14 14 and older

Table 19. Paracetamol + Codeine childrens dose

Weight Age (use only if weight not available) Chronic pain Paracetamol 4-6 hourly (125 mg/5 ml of syrup 2<3 kg 3<6 kg 6<10 kg 10<12 kg 12<16 kg 16<25 kg 3-12 months 12 up to 24 months 24 up to 48 months Over 48 months 03 months 2 ml 2.5 ml 2.55 ml 57.5 ml 7.510 ml 1012.5 ml Chronic severe pain Add codeine phosphate syrup 4 hourly Min dose 0.2 ml 0.3 ml 0.5 ml 1.0 ml 1.5 ml 2 ml Max dose 1 ml 2 ml 3 ml 5 ml 6 ml 8 ml

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Neuropathic pain
Clinical presentation
Patients complain of a burning, hot, tingling sensation similar to pins and needles

Management
Initiate the above steps and add amitriptyline, anticonvulsants, or corticosteroids as described below. Amitriptyline tart with 25 mg at night S Can increase up to 100 mg at night (doctor to review) Give at night as causes drowsiness

Anticonvulsants e.g. gabapentin and carbamazepine hese require a doctor to review and prescribe T

Corticosteroids hese may be useful to enhance pain relief from nerve pain associated with T compression or headaches caused by raised intracranial pressure. They need to be used with caution in HIV positive patients.

Management of Pain

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Management of Pain

Notes
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Appendices

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Appendix 1

Appendix 1: WHO Clinical Staging

of HIV/AIDS for adults and adolescents with confirmed HIV infection (2007)
Clinical stage 1 Clinical stage 2 Clinical stage 3 Asymptomatic Persistent generalized lymphadenopathy (PGL) Moderate unexplained weight loss (<10% of presumed or measured body weight)* Recurrent respiratory tract infections (RTIs, sinusitis, tonsillitis, otitis media, pharyngitis) Herpes Zoster (Shingles) Angular cheilitis Recurrent oral ulcerations Papular pruritic eruptions (PPE) Seborrheic dermatitis Fungal nail infections Unexplained severe weight loss (>10% of presumed or measured body weight) Unexplained chronic diarrhoea for longer than 1 month Unexplained persistent fever (intermittent or constant for longer than 1 month) Persistent oral candidiasis (thrush) Oral hairy leukoplakia (OHL)

Pulmonary tuberculosis (current) Severe bacterial infections (e.g. pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteraemia) Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Unexplained anaemia (< 8.0 g/dL), neutropenia (< 0.5 x 109/L), or chronic thrombocytopenia (< 50 x 109/L)

* Assessment of body weight in pregnant women needs to consider the expected weight gain of pregnancy

Appendix 1

191

Clinical stage 4

HIV wasting syndrome Pneumocystis pneumonia (PCP) Recurrent severe or bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal of more than one months duration) Oesophageal candidiasis Extrapulmonary TB (EPTB) Kaposi sarcoma (KS) Central nervous system (CNS) toxoplasmosis HIV encephalopathy Extrapulmonary cryptococcosis including meningitis Disseminated non-tuberculous mycobacteria infection (NTM) Progressive multifocal leukoencephalopathy (PML) Candida of trachea, bronchi or lungs Chronic cryptosporidiosis (with diarrhea) Chronic isosporiasis Visceral herpes simplex infection Cytomegalovirus (CMV) infection (retinitis or infection of other organs) Any disseminated mycosis (coccidiomycosis or histoplasmosis) Recurrent non-typhoidal Salmonella bacteremia Lymphoma (cerebral or B cell non-Hodgkin) or other solid HIV-associated tumours Invasive cervical carcinoma Atypical disseminated leishmaniasis Symptomatic HIV-associated nephropathy or symptomatic HIV-associated cardiomyopathy

192

Appendix 2

Appendix 2: WHO clinical staging

of HIV/AIDS for children with confirmed HIV infection (2007)
(for persons aged under 15 years with confirmed laboratory evidence of HIV infection: HIV antibody if aged 18 months and above; virological (PCR) testing if aged under 18 months) Clinical Stage 1 Asymptomatic Persistent generalized lymphadenopathy (PGL) Unexplained persistent hepatosplenomegaly Papular pruritic eruption (PPE) Extensive human papilloma virus infection (warts) Extensive molluscum contagiosum Fungal nail infection Recurrent oral ulceration Lineal gingival erythema (LGE) Unexplained persistent parotid enlargement (PPE) Herpes zoster (shingles) Recurrent or chronic URTIs (otitis media, otorrhoea, sinusitis, tonsillitis) Angular cheilitis Unexplained moderate malnutrition or wasting not adequately responding to standard therapy. Unexplained persistent diarrhoea (two weeks or greater) Unexplained persistent fever (intermittent or constant, for longer than one month) Persistent oral candidiasis (after the first 6-8 weeks of life) Oral hairy leukoplakia (OHL) Acute necrotizing ulcerative gingivitis/periodontitis Pulmonary TB Lymph node TB Severe recurrent bacterial pneumonia Unexplained anaemia (< 8.0 g/dL), neutropenia (< 0.5 x 109/L), or chronic thrombocytopenia (< 50 x 109/L) Chronic HIV-associated lung disease including bronchiectasis Symptomatic lymphoid interstitial pneumonitis (LIP)

Clinical Stage 2

Clinical Stage 3

Appendix 2

193

Clinical Stage 4 Unexplained severe wasting, stunting, or severe malnutrition not responding to standard therapy Pneumocystis pneumonia (PCP) Recurrent severe bacterial infection (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) Chronic herpes simplex infection (orolabial or cutaneous of more than one months duration or visceral at any site) Extrapulmonary TB (EPTB) Kaposi`s sarcoma (KS) Oesophageal candidiasis (or candidiasis of trachea, bronchi, or lungs) CNS toxoplasmosis (outside the neonatal period) HIV encephalopathy Cytomegalovirus infection: retinitis or CMV infection affecting another organ, with onset at age > 1 month Extrapulmonary cryptococcosis including meningitis Any disseminated endemic mycosis (coccidiomycosis or histoplasmosis) Cryptosporidiosis (with diarrhoea) Isosporiasis Disseminated non-tuberculous mycobacterial infection (NTM) HIV-associated rectovaginal fistula Cerebral or B cell non-Hodgkins lymphoma Progressive multifocal leukoencephalopathy (PML) Symptomatic HIV-associated cardiomyopathy or HIV-associated nephropathy

194

Appendix 3

Appendix 3:

Enrolment Criteria for ARVs in Adults

Step 1: Start drug readiness training at the same time as clinical workup
(See MSF Adherence counselling guideline, 2007) Start counseling sessions as soon as client meets clinical or CD4 criteria for ARV initiation (see Medical criteria on page 198). Do not wait until the clinical workup is completed. ounselling sessions 1-3 should be completed by the date set by the clinician. C Duration for C sessions to be completed depends on the level of CD4, whether there is TB coinfection or whether HAART/AZT is for PMTCT. The fourth session is given on the day of intiation. ession One: Disclosure and positive living S Session Two: Basics of HIV, CD4 and viral load; cotrimoxazole prophylaxis Session Three: Opportunistic infections, ARV Treatment Plan, Adherence

Encourage client to attend group sessions and to bring treatment buddy (friend or family member). Note that certain patients should be fast-tracked to initiate ART within 2 weeks.
Require fast track (i.e. ART initiation within 2 weeks of being eligible)

Pregnant women eligible for lifelong ART OR Patients with very low CD4 (< 100 cells/L) OR Stage 4, CD4 count not yet available OR MDR/XDR TB Children younger than 1 year

Appendix 3

195

Step 2: Exclude TB. Always ask about TB symptoms

nvestigate for TB if any of the following are present: I Cough 2 weeks Weight loss 1.5kg in 4 weeks Drenching night sweats or fever Chest pain Sputum with or without blood Feeling unwell

If symptomatic, do not commence ARVs until TB has been excluded, if necessary by a doctor. Send sputa for two smears and TB culture if possible. (See pages 8386 for diagnosing TB).

Step 3: Assess clinically

ook for opportunistic infections or other HIV related diseases. See table below L for conditions that need specific action Assess nutritional status, check BMI. Perform pap smear for all women. HIV emergencies are usually due to opportunistic infections. Stabilise the client before starting ARVs. Aim to start ARVs within 2 weeks. Aim to start within 2 weeks. Ideally, patient should start chemotherapy before starting ARVs. But if chemotherapy is not readily available and the CD4 count is low, better to start ART as soon as possible. If > 14 weeks start ARVs as soon as possible with appropriate counselling and adherence support. Aim to start ARVs within 24 weeks (See Table 8 on page 91). For MDR/XDR TB, aim to start within 2 weeks, irrespective of CD4 count.

Acute severe illness CD4 100 Kaposi sarcoma

Pregnancy Tuberculosis

196

Appendix 3

Step 4: Discuss contraception and safe sex

nsafe sex on ARVs can still transmit HIV and carries the risk of re-infection with U different strains of HIV. This can lead to treatment failure. Encourage the use of condoms. Encourage your client to have only one partner. Discuss your clients plan for a family. If required, advise reliable contraception (e.g., injectable contraceptive plus condoms: remember that the dosing interval of injectable contraceptive is changed in case of NNRTI therapy see Appendix 13 on page 230). Efavirenz can cause birth defects. Women of child bearing age who need efavirenz must use reliable contraception. If pregnant, discuss plans for contraception post delivery.

Step 5: Check baseline blood results

ake blood for ALT and creatinine. T heck HBsAg if baseline ALT > 40 (or whenever considering discontinuation of C TDF). Note that routine screening for HBsAg is no longer necessary, since the first-line regimen in S.A. now includes TDF and 3TC (or FTC), provided that the CrCl is > 50 mL/min. Check FBC/differential as baseline but monitor only if on AZT. Calculate the creatinine clearance according to formula. It is essential to calculate the CrCl in patients with age > 50 years, weight < 50 kg, or serum creatinine > 100. If an adult, no need for baseline viral load.

Formula to calculate creatinine clearance

Creatinine Clearance = (140-age in years) x weight in kg 0.82 x creatinine in mol/l (in ml/min)

Then multiply by 0.85 in women

Appendix 3

197

Test

Normal result

Action required if result is abnormal

ALT

< 40 IU/ml

If ALT is abnormally high, consider repeating in order to confirm, and test HBsAg (also investigate alcohol abuse). If ALT > 100, consider using EFV or LPV/r instead of NVP; also consider monitoring the ALT monthly for 3 months. If ALT 41-100, also consider monitoring the ALT monthly for the first 3 months on ARVs.

Hb >10 g/dl

If Hb < 8.0 g/dl, assess carefully for opportunistic infections, especially TB. Consider giving iron and folic acid supplements and repeat Hb in 2-4 weeks. If no OI found, then use tenofovir or d4T instead of AZT when initiating ART.

Neutrophil count

> 1.5 x 109/l

If < 1.0 x 109/l avoid AZT and repeat after 1 month of ARVs. Use TDF or d4T instead.

Hep B s Ag

Negative

Refer to doctor if HBsAg result is positive. Active hepatitis B requires use TDF and 3TC/FTC in the 1st line regimen. Once started, TDF and 3TC/FTC should ideally never be stopped in that person (see page 75). If CrCl < 50 mL/min, repeat to confirm result after correcting possible causes (dehydration, etc). Discuss with doctor. Adjust doses of AZT, DDI, d4t and 3TC as necessary (see Appendix 30 on page 266). Avoid tenofovir in all cases of chronic renal failure (or renal failure that is new in onset, but not resolving).

Creatinine clearance

90 ml/ minute

198

Appendix 3

Step 6: Assess readiness to start treatment once clinical workup and drug readiness training are complete
When yes to all the below, client is ready to start ARVs.

Medical criteria
onfirmation of HIV status, AND C Eligible to start ART CD4 count <200 cells/L irrespective of clinical stage OR CD4 count <350 cells/L In patients with TB/HIV Pregnant women OR

WHO stage IV irrespective of CD4 count OR MDR/XDR irrespective of CD4

2010 S.A. Guidelines recommendations

Tuberculosis and other serious OIs have been diagnosed and treatment started

Social Criteria (not mandatory, but strongly encouraged):

atient is ready to commit to long-term antiretroviral therapy P Patient is willing to disclose HIV status to a person in confidence who agrees to act as the patients Treatment Assistant Patient commits to attend a support group for people on ARVs No alcohol abuse Contraceptives/condoms being used

Adherence Criteria:
atient has presented on time to the last four appointments (includes nurse, P counsellor, and doctor appointments) Patient is able and willing to take tablets regularly* Understands the importance of adherence

*Assessment can be based either on adherence to existing treatment (patient is asked to return with remaining cotrimoxazole tablets, or adherence to TB treatment is assessed if on TB medication) or prospectively by using a substitute (for example, vitamins). However, this should never delay ART.

Appendix 3

199

Step 7: Start ARVs- Regimen 1

iscuss all non-naves who have previously received ARVs with a specialist. D Client must attend 4th drug readiness training session. Always prescribe 3 ARVs (see Appendix 6 on page 205 for usual adult doses, and Appendix 30 on page 266 for dose adjustments in case of renal failure). Give TDF, 3TC or FTC, and EFV unless: In 1st trimester of pregnancy or planning a pregnancy (or unable to use/ refusing contraception): Use NVP instead of EFV (provided CD4 is < 250 and not on treatment for TB). In 1st trimester of pregnancy with CD4 > 250: defer ART until 2nd trimester and initiate on EFV if possible. Otherwise use LPV/r instead of NVP (risk of hepatitis on NVP is much higher if CD4 >250). In 1st trimester of pregnancy, on treatment for TB with CD4 < 250: use LPV/r. The dose of LPV/r should gradually be doubled. Creatinine Clearance <50 mL/min: if renal failure persists despite having ruled out and treated possible causes, replace TDF with AZT (provided Hb > 8.0 g/dL) or d4T (if Hb < 8.0 g/dL); long-term use of d4T should be avoided if at all possible, due to its significant risk of long-term toxicity. If client will start with NVP, remember step-wise induction (Ie. 200 mg OD for first 2 weeks) to reduce the risk of skin rash and hepatitis. Review with client about how to take ARVs and possible side effects. Continue cotrimoxazole +/- multivitamins. Schedule clinic follow up for 2 weeks. 1st Line for adults All new patients needing treatment, including pregnant women Currently on d4T based regimen with no side-effects Contraindication to TDF: renal disease TDF + 3TC/FTC + EFV/NVP For TB co-infection EFV is preferred. For women of child bearing age, not on reliable contraception, NVP is preferred. Remain on d4T if well tolerated. Early change with any toxicity. Substitute TDF if at high risk of lactate toxicity (high BMI, low Hb, older female)

d4T + 3TC + EFV

AZT+ 3TC +EFV/ NVP

2010 S.A. Guidelines recommendations

200

Appendix 4

Appendix 4: Enrolment Criteria

for ARVs in Children
Depending on age: or children < 18 months: a positive PCR test confirmed by a VL > 10,000 F copies/mL (but do not wait for this VL result to initiate ARVs). For children > 18 months: 2 positive antibody tests (either rapid or ELISA)

Confirmation of HIV status

Clinical and Immunological Criteria

Table 21. South African ART eligibility criteria for HIV-infected children (2010)
WHO stage 1 < 12 months* Treat all 12 to 59 months CD4 < 25% or CD4 <750 cells/L 2 Treat all CD4 < 25% or CD4 <750 cells/L 3 4
years of age.

5 years CD4 < 350 cells/L

CD4 < 350 cells/L

Treat all Treat all

Note that WHO (2010) recommends that ART be initiated in all HIV-infected children up to 2 *

Criteria for expedited (fast-track) ART initiation (1 to 2 weeks) Children younger than 1 year CD4 < 100 cells/L (or < 10 %) Stage 4 disease MDR/XDR TB patient

WHO criteria for presumptive diagnosis of HIV infection

Even where DNA PCR testing is not (yet) available, a sick HIV exposed infant should be referred for ART initiation based on the diagnosis of presumptive HIV infection, if he/she fulfils the criteria in the table below:

Appendix 4

201

Criteria for presumptive diagnosis for initiation of HAART in infants < 18 months of age where virological confirmation of infection is not available
Infant is HIV antibody positive (ELISA or rapid test), and Diagnosis of any AIDS-indicator condition(s) can be made, or Infant is symptomatic with 2 or more of the following Oral thrush (recurrent or chronic) Severe pneumonia Severe sepsis Recent HIV-related maternal death or advanced HIV disease in the mother CD4 < 20%

Other supporting factors supporting the diagnosis include:

IMCI definition: a. Oral thrush: Creamy white to yellow soft small plaques on red or normally coloured mucosa which cannot easily be scraped off (pseudomembranous), or red patches on tongue, palate or lining of mouth, usually painful or tender. b. Severe pneumonia: Cough or difficult breathing in a child with chest indrawing, stridor or any of the IMCI general danger signs; i.e., lethargic or unconscious, not able to drink or breastfeed, vomiting, and presence or history of convulsions during current illness; responding to antibiotics. c. Severe sepsis: Fever or low body temperature in a young infant with any severe sign such as fast breathing, chest indrawing, bulging fontanel, lethargy, reduced movement, not feeding or sucking breast milk, convulsions

ARVs in a sick infant who fulfils criteria for presumptive diagnosis of HIV infection. Start ARVs! Do not wait for the 6th week to do a PCR in a sick child for whom a presumptive diagnosis of HIV has been made!

REMEMBER Do not wait for DNA PCR results to start

202

Appendix 4

Social Criteria
(used in the MSF Khayelitsha Project; may require changes for other settings): ust have an adult caregiver who is able to administer medication M Disclosure to another adult living in the same house is to be encouraged so that there is someone else who can help with the childs ART. Caregiver is ready to commit to a support group for caregivers of children on ARVs.

Adherence Criteria
hild has presented with caregiver on time to the past 4 visits. C Child is being given current medications (cotrimoxazole or TB meds) regularly. ll HIV-positive children should be on cotrimoxazole prophylaxis, and the A adherence will be assessed. The following 4 key questions should be addressed: Who will be administering the medications What medications will be given When will medications be given How will medications be given

Baseline Clinical and Laboratory Investigations prior to Initiation of ART in Children

Childs height and weight Clinical staging Screening for TB symptoms Developmental level CD4 count, or CD4 % if < 5 years Viral load (where available) FBC for all children at baseline ALT (if planning to use an NVP-based regimen)

Appendix 5

203

Appendix 5: Different Classes of

ARVs and General Rules
Classes of ARVs
ARVs can be classified according to the different steps where they interrupt the lifecycle of HIV (thereby stopping the replication of HIV).

NRTIs (Nucleoside or Nucleotide Reverse Transcriptase Inhibitors)

hey hinder the enzyme reverse transcriptase T They include: TDF (Tenofovir) 3TC (or the closely-related FTC) AZT ABC (Abacavir) D4T DDI

NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors)

lso hinder reverse transcriptase but in a different way from NRTIs A They include evirapine N Efavirenz

PIs (Protease inhibitors)

inder the enzyme protease H They include Kaletra (= Lopinavir boosted with ritonavir = LPV/r) Aluvia (= same as Kaletra, but in tablet formulation that does not require refrigeration) Ritonavir (RTV): always given in association to other PIs, in a small dose, just to boost their concentration in the blood Atazanavir (ATV)

204

Appendix 5

Some GENERAL RULES about ARV use:

1. Use EFV instead of NVP if a person is taking TB medication (note that EFV is also preferred in any patient with a higher base-line, E.g. CD4 > 250 in females and > 400 in males*). 2. Dont use EFV if a woman is in the first trimester of pregnancy or at risk of becoming pregnant (i.e. not using reliable contraception). 3. Dont use EFV in children less than 3 years or weighing less than 10 Kg. 4. Dont use TDF if the patient has a CrCl < 50 mL/min, or is younger than 15 years of age. 5. When starting NVP (or re-starting after an interruption lasting > 1 week), use lead-in dosing in order to reduce the risk of side effects: give NVP once a day for the first 2 weeks, and if no side effects, then increase it to twice daily. 6. Dont use AZT if Hb< 8.0 g/dl. 7. Some ARVs are adjusted for weight in adults (EFV and DDI). checked at every visit as the child grows! 9. Some ARVs require lower dosing in the presence of chronic renal failure, based on the Creatinine Clearance (see Appendix 30 on page 266). 10. Some ARVs are available in combinations, which reduce the number of pills a person must take every day, and therefore help to improve adherence. Examples include a double combination of TDF + 3TC, AZT + 3TC, D4T + 3TC and a triple combination of TDF + 3TC + EFV, D4T + 3TC + NVP, AZT + 3TC + NVP. 11. Dont use D4T and AZT together in the same regimen! 12. Dont use D4T if a person already has severe peripheral neuropathy!

8. All ARVs are adjusted for weight in children, so dosing needs to be double-

Higher baseline CD4 counts (> 250 cells/L in a female, and > 400 cells/L in a male) are associated with a much higher risk of NVP-induced hepatitis/allergy!

Appendix 6

205

Appendix 6: The Antiretrovirals

ARV TDF (Tenofovir) ABC (Abacavir) Availability 300 mg tablets Usual Adult Dose* 300 mg OD Usually very well-tolerated. CrCl must be > 50 ml/min. Not to be used if < 15 years. Syrup (20 mg/ ml) 300 mg tabs 3TC (Lamivudine) Syrup (10 mg/ ml) 150 mg tabs (also in combo with AZT, D4T or TDF) FTC Usually in fixed-dose (Emtricitabine) combination with TDF AZT (Zidovudine) Syrup (10 mg/ ml) 100 mg tabs 300 mg (also in combo with 3TC) DDI (Didanosine) 25, 50, 100 mg tabs 250, 400 mg caps (enteric coated) D4T (Stavudine) 400 mg once daily TAKE ON AN EMPTY STOMACH. if > 60 kg; use 250 One hour before or two hours after mg if < 60 kg food. Disperse 25 mg and 100 mg tabs in water (or chew). At least 2 tablets of appropriate strength must be used at any one time for adequate buffering. All adults should now receive 30 mg of d4T, regardless of weight. Syrup must be refrigerated. Capsules may be opened (children). Watch for possible side effects of high lactate, peripheral neuropathy and lipodystrophy. 150 mg twice daily or 300 mg OD 300 mg twice daily Potential for severe hypersensitivity reaction (see page 213). No food restrictions. Tablet may be crushed (children). Normally well-tolerated. Specifics

200 mg OD

Normally well tolerated. Analogue of 3TC.

300 mg twice daily

Capsules may be opened (children). Watch for possible side effect of anaemia.

Syrup (1 mg/ml) 30 mg twice daily for all adults 15 mg caps 20 mg 30 mg

206

Appendix 6

NVP (Nevirapine)

Syrup (10 mg/ ml) 200 mg tabs

200 mg once daily for the 1st 2 weeks, then 200 mg twice daily

Tablet may be crushed (children). Watch for rash and hepatitis. Nevirapine induces liver enzymes responsible for its own metabolism. Stepwise introduction helps to reduce the risk of skin rash and hepatitis. Interacts with Fluconazole and TB meds. Taken at night to limit side effects. Avoid taking with fatty foods. Capsules may be opened (children). Tabs may not be chewed, divided or crushed. Avoid in 1st trimester of pregnancy (women must be on reliable contraception). Combination of Lopinavir/ritonavir. Tabs must be swallowed whole and not chewed, divided or crushed. Syrup and caps (not tabs) must be taken with food to enhance absorption and refrigerated until dispensed. Do not open capsules. Does not have to be taken with food If patient is on rifampicin-containing TB regimen, the dose of LPV/r must be doubled or super-boosted with additional ritonavir. To be stored at < 25C (but keep RTV tabs in the fridge). To be taken with food. Always give boosted dose if associated with use of TDF. Contraindicated in those needing > 20 mg a day of omeprazole. Should not be taken together with anti-acid medications (take ATV 2h before or 1h after). Common side effect is jaundice. Cases of allergic rash (usually not severe) and nephrolithiasis have been reported.

EFV (Efavirenz)

50 mg tabs or caps 200 mg tabs or caps 600 mg tabs

600 mg at night if > 40 kg; use 400 mg if < 40 kg

NB: if on rifampicin, 600 mg should be prescribed. 400/100 mg (3 caps) twice daily

Kaletra (Lopinavir/ ritonavir)

Syrup (80/20 mg/ml) 125 mg tabs LPV 133 mg/r 33 mg caps

Aluvia = heat-stable Lopinavir/ ritonavir (LPV/r) ATV (Atazanavir)

250 mg tab (LPV 400/100 mg (= 2 tabs) twice daily 200 mg/r 50 mg)

150 mg tabs, 200 mg tabs

300 mg (2 tabs of 150 mg) OD, together with 1 cap of 100 mg ritonavir (boosted ATV) OR 400 mg (2 tabs of 200 mg) OD

Notes: * Paediatric dosages for all of the above ARVs can be determined using childrens weights. See Appendix 9 for an example of a simplified table showing weight ranges and the appropriate dosages.

Appendix 7

207

Appendix 7: Typical ARV regimens

for adults
1st line ARV regimens for adults.
Although the 2010 S.A. Guidelines recommend TDF + 3TC + EFV/NVP for new initiations, there are many different possible ARV regimens (combinations of individual ARVs). In a first-line regimen, we usually use two NRTIs together with one NNRTI. 2 NRTIs 1 NNRTI

Tenofovir
Dose: 300 mg once daily Not contraindicated in pregnancy or

EFV
Especially if on TB meds 600 mg at night if > 40 kg or on rifampicin (or 400 mg if < 40 kg) or

AZT
Use in pregnancy if TDF is contraindicated for any reason. Dose: 300 mg twice daily or

3TC
+ 150 mg twice daily or 300mg once daily with TDF +

NVP
Especially in pregnant women in the first trimester (or if not on reliable contraception) Dose: 200 mg once daily for the first 2 weeks, then 200 mg twice daily Avoid if CD4 > 250 (female) or > 400 (male) Avoid if ALT > 100 at baseline (in which case ALT should be repeated, HepB sAg should be checked & patient referred to doctor for initiation).

D4T
Dose: 30 mg twice daily Use only if TDF and AZT are contraindicated

208

Appendix 7

Examples of acceptable first-line regimens for adults:

enofovir + 3TC + EFV (These can all be given once daily) T Tenofovir + 3TC + NVP morning dose: 3TC + NVP evening dose first 2 weeks: 3TC + Tenofovir; then: 3TC + Tenofovir + NVP

AZT + 3TC + NVP morning dose: AZT + 3TC + NVP evening dose first 2 weeks: AZT + 3TC; then: AZT + 3TC + NVP

D4T + 3TC + EFV morning dose: D4T + 3TC evening dose: D4T + 3TC + EFV

D4T + 3TC + NVP morning dose: D4T + 3TC + NVP evening dose first 2 weeks: D4T + 3TC; then: D4T + 3TC +NVP

First line regimen and pregnancy

EFV is contraindicated during 1st trimester of pregnancy but NVP might also be contraindicated (hepatic disease or previous allergy). Also, NVP is not recommended in pregnant women with CD4 > 250, because of increased risk of toxicity, and during TB treatment. In all those cases, EFV should be replaced by LPV/r, rather than by NVP. (LPV/r is given at double dose during TB treatment: e.g. instead of 400/100 mg BID, give 800/200 mg BID). For a woman in the 1st trimester of pregnancy with TB and a CD4 > 250, consider to wait until the 2nd trimester before starting ART and initiate with EFV. If pregnancy is diagnosed in the first trimester in a woman already well established on EFV, consult the Medicines Information Center (MIC) Hotline. Note that a case could be made for continuing with the established treatment. There is no longer a contraindication to initiation of TDF in pregnant women (provided that CrCl > 50 mL/min), even during the 1st trimester.

First line regimen and TB treatment

If on rifampicin for TB treatment, substitute NVP with EFV for the duration of TB treatment (or gradually double the dose LPV/r). Two weeks after TB treatment finishes, consider changing EFV back to NVP (an induction dose of NVP is not necessary when EFV is changed to NVP), or if the dose of LPV/r was doubled, this can be reduced to the normal dose (also after 2 weeks).

Appendix 7

209

Patients currently on a D4T-based regimen

Patients currently on D4T-based regimen can stay on it as long as it is being well tolerated. D4T should promptly be changed to TDF in case of any D4T-related toxicity (PN, hyperlactatemia, lactic acidosis, lipodystrophy) or in high-risk patients (BMI > 28, TB treatment), provided that the last VL was LDL, and there is no problem with adherence.

Second-line ARV regimen for ADULTS

The second-line regimen we usually use in South Africa consists of two NRTIs together with a PI. Second Line Treatment for adults Zidovudine (AZT) if previously on TDF; or TDF if previously on d4T or AZT AND Lamivudine (3TC) (or FTC) AND Lopinavir + Ritonavir (LPV/r) If surface hepatitis B antigen positive, do not stop TDF; add the above to TDF.
2010 S.A. Guidelines recommendations 2 NRTIs 1 PI

AZT 300 mg twice daily if previously on TDF or TDF 300 mg OD if previously on AZT Heat-stable Aluvia tabs do not need to be taken with food (but the Kaletra capsules do). The patient will thus take: TDF/3TC (or TDF/FTC) once daily or AZT/3TC twice daily, together with LPV/r twice daily. 3TC (Lamivudine) is maintained in the second line regimen due to its potential stabilizing effect on HIV viral replication, even if resistance to 3TC has already developed.
+

3TC 150 mg twice daily or 300mg once daily with TDF

+

LPV/r Aluvia given as 2 tabs twice daily (compared to Kaletra 3 caps twice daily)

210

Appendix 7

When switching patients with hepatitis B infection to second-line regimens, they need to remain on TDF and 3TC! Stopping TDF could cause a severe flare of the hepatitis. Discuss regimen with an HIV specialist. If a patient on LPV/r develops diabetes or severe dyslipidemia (see page 236237 for reference values), refer to the doctor. A change from LPV/r to Atazanavir/ritonavir (ATV/r) could be considered if high cholesterol, raised fasting glucose, or patient unable to tolerate LPV/r due to gastrointestinal side effects.

LPV/r and TB treatment

Patients starting rifampicin should have the dose of LPV/r doubled gradually over two weeks (to 800 mg lopinavir/200 mg ritonavir) twice daily. Alternatively, instead of doubling the dose of LPV/r, additional ritonavir (an extra 300 mg 12 hourly in adults to super-boost the existing dose of Lpv/r) may be given while the patient is taking TB drugs. Continue with double dose LPV/r (or with boosted LPV/r) for 2 weeks after TB therapy stopped If TB is diagnosed while on LPV/r Week 0: Start TB treatment and increase LPV/r to 600 / 150 mg (3 tablets of Aluvia) twice daily Week 1: give LPV/r 800/200 mg (4 tablets of Aluvia) twice daily

If LPV/r needs to be started while on TB treatment Week 0: Start LPV/r 400/100 mg (2 tablets of Aluvia) twice daily Week 1: Give LPV/r 600 / 150 mg (3 tablets of Aluvia) twice daily Week 3: Give LPV/r 800/200 mg (4 tablets of Aluvia) twice daily

In addition to careful clinical monitoring for symptoms of hepatitis, consider routine monitoring of ALT. If ALT rises above 100, refer to the doctor; if ALT > 200, refer to hospital.

treatment options. Failure is almost always due to poor adherence, and every effort should be made to detect and address this early, as re-suppression of the VL is often possible using the same drugs.

REMEMBER Patients failing second line therapy have few

Studies have shown clinical benefit in continuing on second line therapy despite virologic failure; if no options exist, the patient should be left on the failing regimen.

Appendix 8

211

Appendix 8: Antiretroviral
Therapy Regimens for Children
First and second line regimens in children
First and Second line Regimens in children (SA Paediatric National Guidelines 2010) First line regimens < 3 years or < 10 kg Abacavir (ABC) Lamivudine (3TC) Lopinavir/Ritonavir (LPV/r) Following ABC/3TC/EFV in first line >3years and >10kg Abacavir (ABC) Lamivudine (3TC) Efavirenz (EFV) Following d4T (or AZT or ddI) containing regimen in first line (provided that LPV/r was not part of the regimen) Abacavir (ABC) Lamivudine (3TC) Lopinavir/Ritonavir Note to first line regimens: For children on Stavudine not currently having sideeffects, Stavudine may be continued. Abacavir should be substituted for d4T as soon as PN or any lipodystrophy is suspected. Zidovudine (AZT) Didanosine (ddI) Lopinavir/Ritonavir Second line regimens Following a LPV/r based regimen in first line or child <3 years Refer to doctor

212

Appendix 8

Treatment with ARVs and TB drugs in children

ART + rifampicin-based TB treatment in children < 3 years or < 10 kg, or any child on a LPV/r based regimen => Boost LPV/r with additional ritonavir => For older children, double the dose of LPV/r => Change NVP to EFV

>3 years and > 10 kg on NVP based regimen

Additional Ritonavir dose in children taking rifampicin

Extra Ritonavir dose = 0.75 x LPV/r syrup dose in ml (therefore if LPV/r dose = 1 ml, you need to add 0.75 ml of ritonavir, see dosing chart in Appendix 9). Continue with super-boosted LPV/r for 2 weeks after TB therapy stopped.

Notes on prescribing ARVs in children

osing based on weight or body surface area (BSA) D ARV dosing charts based on childs weight are available (See Appendix 9) NVP is prescribed once daily for 2 weeks then twice daily Switch from syrups to tablets or capsules as soon as possible Stavudine syrup cannot be given to those with no access to refrigerator LPV/r syrup denatures unless it is kept in a cool, dry place at a temperature <25 C (and shouldnt stay out of fridge for more than 42 days). Refrigerate if possible. Remember to recalculate doses at each clinic visit according to current body weight and/or body surface area. Giving the child too little medication for his/ her weight will cause him/her to develop resistance faster. Giving the child too much medication for her/his weight may lead to more side effects. Young children who start on a LPV/r based regimen should remain on the same regimen even after reaching 3 years or 10 kg unless a substitution or switch to second line regimen is indicated for reasons of toxicity or treatment failure.

Appendix 8

213

General comments on individual drugs

Abacavir (ABC)
Tablets can be crushed and mixed with a small amount of water or food and immediately ingested. No food restrictions. Once daily dosing is not yet approved for children. Caregivers must be warned about potential (but very rare!!) Hyper-Sensitivity Reaction (ABC HSR) which may include: fever (80% of cases) rash (70%, but often mild, non pruritic and unnoticed) gastrointestinal & respiratory symptoms (18% have cough, pharyngitis, dyspnoea) constitutional non-specific symptoms (myalgia, generalized malaise).

ABC should be stopped permanently if hypersensitivity reaction occurs, and never re-challenged (recurrence might be fatal). Its very easy to mistake a common viral infection for an HSR due to ABC, but the following can help: 1. HSR usually occurs in the 1st 6 weeks after initiation on ABC (mainly 1st 10 days) 2. Symptoms worsen just after every new dose (and with every subsequent dose) 3. Symptoms usually resolve after 48h from discontinuation 4. Never initiate ABC if the patient is already having fever or cough 5. NEVER INITIATE A PATIENT ON NVP AND ABC AT THE SAME TIME!! (In case of severe allergy, it would be then impossible to ascertain the culprit drug, and rechallenge would be too dangerous...). A shift to ABC is allowed when required for example in case of d4T toxicity only if the patient is stable on NVPbased treatment, for more than 6 weeks 6. Decision about stopping ABC should be made by a health care provider (not by the patient himself) 7. The patient has to be given a Patient Alert Card to be shown, in case of symptoms, to any health care provider he/she might consult, to make the HCP aware that he/she is taking ABC.

Lamivudine (3TC)
Well tolerated, no food restrictions, oral solution may be stored at room temperature. Tablets are scored and can be easily divided; may be crushed and

214

Appendix 8

mixed with a small amount of water or food and immediately ingested. Once daily dosing is not yet approved for children.

Lopinavir/ritonavir
Dose is calculated based on lopinavir component. Solution should be taken with food as increases absorption. Oral solution and capsules should be refrigerated but can be stored at room temperature up to 25C for 6 weeks. May need techniques to increase tolerance & palatability: coat mouth with peanut butter, dull taste buds with ice, follow dose with sweet foods. Kaletra capsules are soft and may not be opened or crushed and must be swallowed whole. Aluvia tablets must not be chewed, divided or crushed; swallow whole with or without food. Many drug interactions due to RTV inhibition of cytochrome p450.

Efavirenz (EFV)
EFV is not approved for children <3years or <10kg. Tablets must not be chewed, divided or crushed; swallow whole with or without food e.g. yoghurt or banana. Capsules may be opened and powder contents dispersed in water or mixed with a small amount of food (e.g. yoghurt) to disguise peppery taste and immediately ingested. Food, especially high-fat meals, increases absorption. Best given at bedtime to reduce CNS side-effects, especially during first 2 weeks.

Zidovudine (AZT)
No food restrictions and oral solution may be stored at room temperature. AZT may be used as an alternative first-line drug to Abacavir where ABC is not available or there is a contraindication. Capsules may be opened and powder contents dispersed in water or mixed with a small amount of food (e.g. yoghurt) and immediately ingested. Currently available tablets are not scored. Use with caution in children with anaemia due to potential for bone marrow suppression. Available as 2-in-1 FDC with 3TC and as 3-in-1 FDC with 3TC and NVP.

Didanosine (ddI)
At least 2 tablets of appropriate strength must be used at any one time for adequate buffering. Tablets may be chewed or crushed and dispersed in 30ml water and immediately ingested. Enteric coated tablets (250 mg) are available for once daily use in children > 20 kg. It is recommended to administer ddI on an empty stomach at least 30 minutes before or 2 hours after meals.

Ritonavir (RTV)
Only recommended use at present is as booster for lopinavir/ritonavir when being co-administered with rifampicin-containing TB treatment. Should be taken with food. May be stored at room temperature, limited shelf life of 6 months. May need to use techniques described for LPV/r syrup, to improve tolerance of bitter taste.

Appendix 8

215

Nevirapine (NVP)
Caregivers must be warned about the (small) possibility of a potentially lifethreatening rash during the first 3 weeks of treatment with NVP. Once daily lead-in dosing during the first 2 weeks of treatment reduces the frequency of rash. NVP should be permanently discontinued and not restarted in children who develop severe rash especially if accompanied by fever, blistering or mucosal ulceration. If a mild rash occurs during the induction period, continue once daily dosing and only escalate dose to twice daily once the rash has subsided and the dose is well tolerated. No food restrictions. Tablets can be crushed and mixed with a small amount of water or food and immediately ingested. Avoid NVP if rifampicin is being co-administered. Consider drug-drug interactions.

Stavudine (d4T)
Well tolerated & palatable but oral solution requires refrigeration after reconstitution. Discard after 30 days. Capsules may be opened and powder contents dispersed in water (stable in solution for 24 hours) or mixed with a small amount of food (e.g. yoghurt). See dosing chart for further details. Consider early drug substitution if toxicity e.g. lipodystrophy/lypoatrophy develops. Available as FDC with 3TC as baby/junior Lamivir and with 3TC/NVP as baby/junior Triomune.

216

Target dose

Stavudine (d4T) 1mg/kg/dose TWICE daily Available Sol. 1mg/ml formula- Caps 15, 20, 30 mg tions

Lamivudine (3TC) 4-6 mg/kg/dose TWICE daily Sol. 10mg/ml Tabs 150 mg (scored)

Zidovudine (AZT) 240 mg/m2/dose TWICE daily Sol. 10mg/ml Caps 100 mg Tabs 300 mg (not scored)

Didanosine (ddI) 90-120 mg/m2/dose TWICE daily Tabs 25, 50, 100 mg (dispersible in 30 ml water) Caps 250 mg EC

Abacavir (ABC) 8mg/kg/dose TWICE daily Sol. 20 mg/ml Tabs 300 mg (not scored)

Appendix 9

Efavirenz (EFV) By weight band ONCE daily Caps 50,200 mg Tabs 50, 200, 600 mg (not scored)

Wt. (kg) <3 3-3.9 4-4.9 5-5.9 2 x 25 mg tabs 9 ml 4 ml

Consult with a clinician experienced in paediatric ARV prescribing for neonates (< 28 days of age) and infants weighing < 3 kg 6 ml 3 ml 6 ml avoid 3 ml Dosing < 10 kg not established

Chart for Children (2009)

6-6.9

4 ml

7-7.9 8-8.9 9-9.9 12 ml 1 x 50 mg + 1 x 25 mg am; 2 x 25 mg pm 1 x 50 mg + 1 x 25 mg tabs 7 ml 6 ml

10-10.9

7.5 mg: open 15 mg capsule into 5 ml water: give 2.5 ml & discard rest 10 mg: open 20 mg capsule into 5 ml water: give 2.5 ml & discard rest 15 mg: open 15 mg capsule into 5 ml water

6 ml

200 mg cap/tab

11-11.9 12-13.9 14-16.9 2 caps am; 1 cap pm

20 mg: open 20 mg capsule into 5 ml water 2 caps 1 tab

tab

200 mg cap/tab + 50 mg cap/tab 8 ml 10 ml 1 tab

17-19.9 20-24.9

25-29.9

20 mg am 30 mg pm 30 mg

1 tab am; tab pm 1 tab

2 x 50 mg tabs am; 1 x 50 mg + 1 x 25 mg pm 2 x 50 mg tabs 1 x 100 mg tab + 1 x 25 mg tab twice daily OR 1 x 250 mg EC cap once daily

Appendix 9: Antiretroviral Drug Dosing

200 mg cap/tab + 2 x 50 mg cap 200 mg cap/tab + 3 x 50 mg cap 2 x 200 mg caps/ tabs 600 mg tab

30-34.9 35-39.9

> 40

Compiled by J. Nuttall & S Raiman, Red Cross Childrens Hospital, Cape Town. Adapted from World Health Organization, 2006 & 2008.

Nevirapine ** ONLY as booster for LPV/r when on Rifampicin TWICE daily Sol. 80 mg/ml Sol. 40/200mg/5ml Tabs 80/400 mg (scored) 2.5 ml 2.5 ml Sol. Tabs (B Co) Available formulations Weight < 3 mg ONCE daily ONCE daily

Ritonavir boosting (RTV)

Co-trimoxazole

Multi-vitamins

Target dose

150 mg/ m2/dose * TWICE daily

Sol. 10 mg/ml Tabs 200 mg (scored)

Lopinavir/ritonavir (LPV/r) 300/75 mg/ m2/dose LPV/r TWICE daily Sol. 80/20 mg/ml Tabs 200/50 mg, 100/25 mg

Consult with a clinician experienced in paediatric ARV prescribing for neonates (< 28 days of age) and infants 5 ml 1 ml ** 1ml 1.5 ml ** 1.2 ml 5 ml OR tab

8 ml

10 ml

2 ml twice daily OR 100/25 mg tabs: 2 tabs am; 1 tab pm ** 2 ml 10 ml OR 1 tab

** 1.5 ml

5 ml

1 tab am; tab pm ** 2.5 ml

3-3.9 4-4.9 5-5.9 6-6.9 7-7.9 8-8.9 9-9.9 10-10.9 11-11.9 12-13.9 14-16.9 17-19.9 20-24.9

1 tab

** 3 ml

25-29.9

2 tabs

1 tab

30-34.9

Appendix 9

2.5 ml twice daily OR 100/25 mg tabs: 2 tabs twice daily 3 ml twice daily OR 100/25 mg tabs: 3 tabs am, 2 tabs pm 3.5 ml twice daily OR 200/50 mg tabs: 2 tabs am, 1 tab pm 4 ml twice daily OR 200/50 mg tabs: 2 tabs am, 1 tab pm 5 ml twice daily OR 200/50 mg tabs: 2 tabs twice daily ** 4 ml

35-39.9 > 40

217

218

Appendix 9

* A lead-in dose of nevirapine is given for the first 14 days of treatment equivalent to half of maintenance dose i.e. usual maintenance dose but given but given once-daily. Increase to full maintenance dose after 14 days if no rash develops.

Body Surface Area (BSA) m2 =

Mass (kg) x Height (cm) 3600

ARV X X X X X X Only if baseline ALT > 40 (but mandatory before stopping TDF for any reason) X (children only) X X X X X X X X X X annually annually only in children X X X annually Required only for AZT at 1, 2, 3, and 6 months X X X X X X X X X X X 6-monthly annually X X X X X X X X X X 6-monthly X If adherence problems

Medical Intervention

Before ART Day of ART initiation initiation

Wk Wk Mo Mo Mo Mo Mo 1 2 1 2 3 6 12

Mo Mo 18 24

Thereafter

Informed Consent

Treatment Assistant (preferred but not mandatory)

Clinical Exam (history, weight, physical)

All

Monitor for possible side effects

ARVs

CD4 cell count

Patient on ARVs

FBC

HBsAg

Appendix 10:

Viral load should be done on children prior to ART initiation (compared to adults, where VL is only done after 6 months on ART)

Tenofovir Creatinine

AZT

FBC + differential

d4T

Lactate

Lactate should be checked if weight loss, PN, or symptoms of high lactate after 4-6 months on d4T Fever +/- rash on ABC requires immediate clinical assessment to rule out a Hypersensitivity reaction (HSR) Only if suggested by clinical condition X Only if suggested by clinical condition (rash, jaundice or other symptoms of hepatitis) X X
(child)

Monitoring a

ABC

Rule out HSR

EFV

ALT*

NVP

ALT*

Appendix 10

Lpv/r

Lipids (Chol/TG) fasting

X
(child)

annually only in children X

Lpv/r

Glucose fasting

219

* If baseline ALT is abnormal, then it should be checked monthly for 3 months if patient is started on NVP or EFV.

220

Appendix 10

Examples: 1. All patients starting TDF + 3TC + EFV should get the following baseline bloods before starting ARVs: FBC + differential, CD4 count, creatinine 2. All patients on AZT + 3TC + NVP at 1 month should get the following bloods: FBC + differential

3. All patients on Tenofovir + 3TC + NVP at 6 months should get the following bloods: Creatinine, CD4 and viral load.

Appendix 11

221

Appendix 11: Early and late side

effects of ARVs
Symptom Rash

Early side effects possible in the first 3 months

Think of Drug-related cause (NVP, cotrimoxazole, or TB drugs) If abdominal pain, think of pancreatitis or hepatitis Pancreatitis Hepatitis Important Actions Grade the rash Treat according to Grade See sections below

Nausea

Vomiting

Correct any dehydration Check Lipase and ALT Metoclopramide as required if severe

Abdominal Pain

Pancreatitis Hepatitis

Check Lipase Check ALT Investigate for TB Send stool sample for investigation Refer for L.P. Consider changing Efavirenz to another ARV (if no meningitis found) Check Haemoglobin (Hb) If confirmed, stop ABC immediately and never re-try again! If doubtful, allow the pt. to take one more dose and watch him/her carefully.

Weight loss

Not a side effect, but probably an undiagnosed OI: (TB, Chronic diarrhoea) Rule out infection before blaming this on Efavirenz!

Confusion

Weakness Fever, constitutional symptoms, cough, sore throat, rash...

Anaemia (if on AZT) HSR to ABC (See page 213).

222

Appendix 11

Late side effects possible after 3-6 months on ARVs

Symptom Nausea +/- Vomiting Think of High lactate Important Actions Check lactate level (+ refer to doctor if lactate level high) Weight Loss Tuberculosis High lactate Abdominal Pain High lactate Hepatitis Pancreatitis Shortness of breath High lactate with lactic acidosis Peripheral Neuropathy (due to D4T) Lipodystrophy Anaemia (if on AZT) TDF toxicity Investigate for TB Check lactate level Check lactate level Check ALT Check Lipase level Check lactate level and refer to doctor

Painful, cold feet

Grade the P.N. and treat accordingly Consider stopping D4T Change D4T to another ARV Check Haemoglobin (Hb) After having ruled out treatable causes of acute renal insufficiency (dehydration due to fever, diarrhea, protracted vomiting, etc), change TDF to AZT.

Fat redistribution Weakness Creatinine Clearance < 50 ml/min

Symptom/ likely ARV responsible

Grade 1

Grade 2

Grade 3

Grade 4

Peripheral neuropathy (painful feet, numb fingers or face) This stage of neuropathy shouldnt be reached anymore now, thanks to early change from DDI and D4T to TDF or AZT. - If still on D4T or DDI, see management as for grade 3 - If already shifted to AZT or TDF and still progressing consider other causes (alcohol intake, INH or other anti-TB drugs, poorly controlled diabetes, renal insufficiency...) - Consider also that PN, whatever the cause, needs a long time to improve - In serious or atypical cases of neuropathy (ie, rapidly ascending muscular weakness or pain), check for high lactate.

Mild, does not worry patient

Moderate, bothers patient Symptoms day and night OR pt. not No relief with Amitriptyline, with (Patient adherent and adherent OR last VL detectable functional impairment (patient latest VL = LDL) has difficulty walking, etc)

Appendix 12: Antiretroviral therapy:

grading of side effects and management

d4T, ddI

-No treatment is needed

-Change from d4T to TDF, -Try to delay TDF substitution until provided that CrCl is > 50 all adherence problems have been mL/min solved and VL is undetectable (thats to avoid development of -Start Paracetamol TDF resistance): in the meantime, and Pyridoxine 25mg replace d4T with AZT 300mg BID nocte. If no relief, add anyway, and continue with other Amitriptyline 25mg nocte ARVs (DON T FORGET: baseline FBC, and monthly thereafter for first -Reassure the patient (after substitution of d4T 3 months and at 6 months) or DDI, the neuropathy -If Amitriptyline relieves symptoms will take some months to dose can be increased up to 100mg improve)

Appendix 12

223

224

Symptom/ likely ARV responsible Minimal food intake (>48hrs) -Give ORT -**Consider stopping all ARVs if amylase> 4 x N and/or ALT > 400 -Also consider lactic acidosis if patient has been on d4T for more than 3 months, and do blood lactate level Vomits all foods & drinks -Give ORT -**Consider stopping all ARVs if amylase >4xN and/or ALT >400 -Also consider lactic acidosis if patient has been on d4T, DDI or AZT for more than 3 months, and do blood lactate level Mood changes or persistent disturbing dreams -Rule out OI; refer to doctor -Consider changing EFV to NVP Patient too weak for outpatient treatment with no known OI

Grade 1

Grade 2

Grade 3

Grade 4

Appendix 12

Abdominal pain & nausea

Mild and transient <24hr

Food intake decreased (24-48hrs)

-Encourage frequent small meals

d4T, ddI: pancreatitis, -No treatment lactic acidosis needed, but have patient return early NVP: liver damage if pain worsens

-Give Metoclopramide 10mg every 8 hours

-Refer urgently to hospital where all ARVs will be stopped if toxic hepatitis or pancreatitis -Put up normal saline IV if available

-Take blood for *Amylase, Lipase and ALT and reassess in 2-3 days

Vomiting

<3x per day and <1 week

<4 per day or > one week

Shock or too weak for out-patient treatment -Put up normal saline IV if available, for rehydration -Refer to hospital (where ARVs will be stopped if necessary).

d4T, ddI: pancreatitis, -Reassure patient, lactic acidosis but have patient return early if NVP: liver damage worsens

-Give ORT & encourage frequent small meals

-Give Metoclopramide 10mg every 8 hours

-Give ORT

-Take blood for *Amylase, Lipase and ALT and reassess in 2-3 days

Psychological

Dizziness

Vivid dreams

Acute psychosis, hallucinations

EFV

-Reassure patient

-Reassure patient

-Confirm EFV is taken at night

-Symptom will go away after few days -Refer for LP

-Refer to hospital, where all ARVs will be stopped, if no other cause of psychosis is found. (Consider tail protection **) -Do LP to rule out meningitis -Only restart ARVs when symptoms resolved, now use NVP instead of EFV

-Take EFV on empty stomach

Symptom/ likely ARV responsible Blisters or moist loss of skin - Refer to doctor on same day, check ALT, **Stop NVP/EFV. -Give Chlorpheniramine 4mg 8h, monitor daily. -When symptoms resolved restart ARVs, NVP (if due to EFV) or EFV (if due to NVP) Generalised Urticaria Anaphylaxis (patient in shock) --Resuscitate patient give adrenaline 1:1000 solution 1 ml IM (age > 15 years); 1:10 000 solution 0,1 ml/kg IM (child < 15; max 10 ml) -Stop all ARVs - Refer to hospital: ARVs can be restarted once pt. stable but now use LPV/r instead of NNRTI (EFV contraindicated because of possible cross-reactivity) >400 -Stop all ARVs -Refer to hospital, LFT patient is in first trimester of pregnancy) -Monitor ALT closely (weekly until decrease of ALT) -Restart ARVs with EFV (unless patient is in first trimester of pregnancy) -Refer to hospital and stop all ARVs -ARVs can be re-started once patients stable but now use Lopinavir/r instead of NVP or EFV Rash effects mucous membranes or eyes, sloughing of skin

Grade 1

Grade 2

Grade 3

Grade 4

Skin rash

Red, itch

Mac-pap rash or dry scales

NVP (more common) or EFV

-Give Aqueous cream and 1% Hydrocortisone or Betamethasone

Also TB meds and cotrimoxazole!

-Reassure patient, but have patient return early if worsens

- check ALT

- ask to return early if worsens, or abdominal pain develops

Allergic reaction

Itch, no rash

Some urticaria (red swollen lesions)

NVP (more commonly)

-Give Aqueous cream and 1% Hydrocortisone or Betamethasone

EFV

Reassure patient, but have patient return early if worsens -Give 1% Hydrocortisone or Betamethasone

-Check ALT, and refer to doctor to decide about stopping ARVs -Give Chlorpheniramine 4mg 8 hourly temporarily -Give Chlorpheniramine 4mg 8h & Check ALT, and reassess in 2-3 days Promethazine 25mg nocte

ALT (U/L) =

50-100

100-200

200-400 -**Stop NVP -Continue ARVs with EFV (unless

NVP (more commonly)

Continue ARVs, but -Reassure the patient monitor 2-weekly -Continue ARVs if no other problem

EFV

-Monitor ALT again after 14 days

Also TB meds and cotrimoxazole!

Appendix 12

-Consider the possibility of NRTIinduced steatohepatitis (especially in pt. on d4T for many months), which may be accompanied by high lactate.

-In children, consider the possibility of ARV over-dosage (check if dose adequate for weight)

225

226

Symptom/ likely ARV responsible >1,5 2 x ULN -Examine the patients abdomen -Continue ARVs if no other problem -Monitor Amylase and Lipase again after 14 days -Repeat blood tests and refer to doctor >2-5 ULN >5,0 x ULN

Grade 1

Grade 2

Grade 3

Grade 4

If *Amylase 4X N and Lipase= >1 1,5 x Upper Limit Normal

Appendix 12

d4T, ddI

AZT, 3TC

Continue ARVs if no other problems, but monitor

-Stop all ARVs (Where possible stop d4T/AZT and 3TC, and consider giving Aluvia 4 tablets BD for 10 -Rule out alcohol abuse days for tail protection = double -Rule out hypertriglyceridemia dose**) (some reactive stripes for -Refer to hospital lactate measure it as well) -If abdominal pain: Stop all ARVS -When pancreatitis has resolved, restart ARVs with TDF or AZT instead of D4T <6,5 -Stop AZT, replace by TDF (see column to the left) or d4T -Refer to hospital or doctor, consider blood transfusion

Anaemia (Hb in g/dl) -Reassure patient, check for other causes of anaemia (rule out TB!), supplement with iron and vitamins -Monitor FBC again after 1 week: if Hb continues to drop consider replacing AZT by TDF or d4T (or reduce AZT to 200mg BD)

8-9,4

7-7,9

6,5 6,9 -Consult with doctor and look for other causes of anaemia (rule out TB!), supplement with iron and vitamins -Replace AZT by TDF (if not contraindicated and recent VL undetectable) or by d4T 30mg BD -Keep monitoring Hb 2-weekly until normalized

AZT

-Continue ARVs, but monitor

Neutropenia 0,75-1,0 x 106

1-1,5 x 106

0,5-0,75 x 106 -Consult with doctor, supplement with folic acid and stop CTX -Keep monitoring after 14 days, if further drop replace AZT by TDF (see column to the left) or d4T

<0,5 x 106 -Stop AZT, replace by TDF or d4T (see column to the left), give folic acid supplements and stop CTX -Refer to doctor

AZT

-Continue ARVs, but monitor

-Reassure pt. and continue ARVs, give folic acid supplements -Monitor FBC again after 14 days: if WBC continues to drop consider replacing AZT by TDF (if no contraindication and VL undetectable) or d4T.

Symptom/ likely ARV responsible Fat accumulation or atrophy appeared after few months from initiation on ARVs, not related to any other possible reason and confirmed by the health care provider

Grade 1

Grade 2

Grade 3

Grade 4

Lipodystrophy/lipoatrophy

No symptoms

Fat accumulation in breasts, abdomen and neck. Fat loss in face, limbs and buttocks. - Reassure pt. and continue regimen - As soon as VL is found undetectable and pt. doesnt raise any doubt about adherence, move to TDF Symptomatic hyperlactatemia (fatigue, abdominal pain, PN, tachycardia, LOW) Lactate: 2-4 Lactate >4 or RR>20 Lactic acidosis syndrome (may be fatal)

d4T

Hyperlactatemia/lactic acidosis

Symptoms of high lactate present, but Lactate: < 2.0

(Abdominal symptoms: nausea, vomiting, no appetite, abdominal pain and distention, fatigue. Liver dysfunction)

d4T

-Continue ARVS

-Hospitalise, rehydrate, stop all ARVs (give LPV/r tail protection**) -Never re-challenge with D4T or AZT or DDI -Rechallenge with TDF/3TC + NNRTI or PI, once lactate normalized and pt. is fine again

-Can repeat lactate if any risk factor present ( female, >75kg, BMI>28) -Keep monitoring lactate weekly until lactate normalized -If ARVs were stopped, rechallenge with TDF/3TC + NNRTI or PI, once lactate has normalized -Always refer to doctor 400-750 Refer to doctor Continue ARVs

-Change d4T to TDF (if CrCl > 50 mL/ min and pt. is not failing treatment: if not so, stop all ARVs**)

Triglycerides mg/dl

750-1200 Refer to doctor Continue ARVs

>1200 Refer to doctor Continue ARVs

Appendix 12

Cholesterol

Refer if LDL> 130 mg/dl or >3.36mmol/l Continue ARVs

227

228

Appendix 12

* Note: Amylase should be requested at the health centre level if Lipase not available. Lipase then done at hospital if amylase >4 X normal ** TAIL-PROTECTION REGIMENS for NNRTI drug interruption: Whenever we have to stop EFV or NVP, its advisable to continue AZT/3TC or d4T/3TC for 7 days, to avoid emergence of HIV resistance. Likewise, when we have to stop ALL ARVs (e.g. in case of lactic acidosis), its better to give a tail-protection with a double dose of Aluvia (that is 4 tabs BD) for 710 days. A double dose is given because of an interaction between LPV/r and the NNRTI. Note: Since TDF has a longer half-life than d4T or AZT, it can better protect the tail of NNRTIs, meaning that the duration of tail protection can be shortened when having to stop EFV or NVP in those taking TDF/3TC or TDF/ FTC. Stopping TDF in a HBsAg+ pt. is contraindicated and a doctor should manage the case. In case of a life-threatening condition (but different from drug-induced hepatitis!! E.g. emergency surgery), necessitating interruption of all ARVs, withdrawal of TDF for few days is allowed, under surveillance. Re-introduce as soon as possible.

Appendix 12

229

Recommended substitutions for specific severe side effects

Regimen TDF/3TC/NNRTI AZT/3TC/NNRTI D4T/3TC/NNRTI Toxicity TDF: renal damage (CrCL < 50 ml/min measured twice) AZT: severe anemia D4T: peripheral neuropathy OR lactic acidosis OR lipodystrophy EFV: persistent CNS toxicity Drug substitution AZT/3TC/NNRTI* TDF/3TC/NNRTI TDF/3TC/NNRTI (but only if VL below limit of detection and no adherence problems) Change EFV NVP **

NRTI/3TC/EFV

NRTI/3TC/NVP

NVP: grade 3 and 4 hepatotoxicity or grade 4 skin toxicity (see also p. 225) - NVP: grade 3 skin toxicity (see also p. 225)

Change NVP PI (LPV/r)

Change NVP EFV if pt. can be hospitalized; if not PI

* Permanently stopping TDF in patients with positive HBsAg is contraindicated and might lead to severe reactivation of hepatitis B: refer to doctor ** When changing from EFV to NVP, no need to start with NVP half dose (200mg OD) unless EFV had already been stopped for more than one week (give NVP 200 BID as of the 1st day).

230

Appendix 13

Appendix 13: Common drug

interactions
Rifampicin
Co-administration with NVP or PIs reduces ARV drug concentrations. EFV is drug of choice in case of co-administration of TB treatment. In case LPV/r is used, the dosage needs to be doubled (return to the normal dose 2 weeks after the end of anti-TB treatment) or add ritonavir syrup (see page 210). (Recommendations in MSF programmes, November 2007),

Oral contraceptive pills

Their effectiveness is reduced if taken with NVP, EFV or any of the PIs. Women should be informed to use a barrier method such as condoms. The effectiveness of Depot contraception may also be affected by NNRTIs. The interval between injections should be reduced from 12 to 8 weeks for medroxyprogesterone (Depo-Provera) and from 8 to 6 weeks for norethisterone (Noristerat).

Ketoconazole
Blood levels are significantly lowered with use of NVP. Use of the systemic antifungal agent fluconazole is preferred.

Benzodiazepines
Should be avoided with EFV due to increased risk of sedation.

Carbamazepine
Co-administration of carbamazepine with NVP, EFV or LPN/r should be avoided due to changes in drug levels in the blood. In case of PN due to D4T, vitamin B6 and/or amitriptyline should be used instead.

Herbal or traditional treatments

Over-the-counter and traditional herbal treatments should be avoided with all ARV drugs as they might lead to inadequate drug concentrations. For example St Johns Wort, a popular herbal remedy for treating mild depression, reduces the plasma concentrations of all ARV drugs.

Warfarin
Interactions can occur between warfarin (used in persons to help prevent clot formation), rifampicin, the PIs, and NNRTIs. Frequent, careful monitoring of the INR is recommended.

Appendix 14

231

Appendix 14: Key points for

Ask
If this is the first visit: Review medical history; particularly for TB, other opportunistic infections, and chronic problems. For all visits: How have you been? What problems have you had? Have you had any of the following? If yes, ask for how long: Headache? Fever? Night sweats? Cough? Nausea or vomiting? Poor appetite? Mouth sores? Abdominal pain? Diarrhoea? New skin rash? Fatigue? Signs of STI? Tingling, numb, or painful feet/legs? Any other pain? If yes, where?

clinical review of symptoms and signs

Look
In all patients: Look for pallor. If present check haemoglobin level. Look at the whites of eyes: are they yellow? If CD4 < 100, examine retinae through dilated pupils Look for oral thrush Listen to the lungs and palpate the abdomen Weigh, calculate, and record weight gain or loss. If weight loss >10%, ask for food intake and assess carefully for TB symptoms. Take the height of adults at the first consultation and calculate BMI. Take the height of children at each consultation and calculate the ratio W/H. Estimate adherence If the patient is sad or has lost interest, assess for depression.

Have you needed urgent medical care? If yes, ask for record/ diagnosis Which medications are you taking and how often? Assess adherence (if on opportunistic infection prophylaxis and/or ART) What problems have you had taking the medicines? How are you taking the medicines? Taking any other drugs (traditional remedies, TB, ARV, illicit drugs, etc) How are things at home? Who knows about your diagnosis and how do you feel about someone attending with you for appointments? Is there anything else you would like to talk about? Access to/need for/family planning?

If any new symptoms: Examine the relevant system and do further assessment of symptoms. Measure temperature. Check lymph nodes Look for a rash Look for evidence of violence.

Recommendations in MSF programmes, Nov 2007; Adapted from: Chronic HIV care with ARV Therapy: Integrated management of adolescents and adults illness interim guide for first-level-facility health workers. Geneva, WHO, December 2003.

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Appendix 15

Appendix 15: Karnofsky Score

The Karnofsky Score is one way to measure a persons ability to perform activities of daily living. As a person gets sicker, they become less active and less able to care for themselves. As their performance suffers, their Karnofsky Score decreases. Able to carry on normal activity; requires no special care 100 90 Normal; no complaints of disease Able to carry on normal activity; minor symptoms or signs of disease 80 Able to carry on normal activity with some effort; some symptoms or signs of disease Cares for self; unable to do normal activity or to do active work Requires occasional assistance but is able to care for most of own needs Requires considerable assistance and frequent medical care Disabled; requires special care and assistance Severely disabled; hospitalisation indicated although death not imminent Very sick; hospitalisation necessary; active supportive treatment necessary Moribund, fatal processes progressing rapidly Dead

Unable to work; able to live at home and care for most personal needs; requires a varying amount of assistance

70 60

50 Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly 40 30

20

10 0

Appendix 16

233

Appendix 16: Desensitization

with cotrimoxazole
(D.Wilson, 2000) Give cotrimoxazole syrup (which contains 40 mg TMP / 200 mg SMX per 5 ml) as follows: ml daily for 3 days 1 Then 2 ml daily for 3 days Then 5 ml daily for 3 days Then 10 ml daily for 3 days Then 20 ml daily for 3 days Then 1 tablet daily for 3 days Then 2 tablets daily Can be used when side effects to cotrimoxazole are not severe

Note that up to 70% of patients may again tolerate cotrimoxazole after the above desensitization under surveillance. Desensitisation should not be attempted in children

234

Appendix 17

Appendix 17: Introduction to the

interpretation of blood results
Explanation of various tests
Liver function tests:
lbumin is a protein in the blood. Severe damage to the liver could cause the A albumin levels to be low. Malnutrition or severe infection could also cause a low albumin (hypoalbuminemia). Other tests such as ALT, AST or GGT are also commonly referred to as liver function tests although in reality, they are better indicators of liver inflammation than liver function. Some drugs like NVP, Rifampicin and Phenobarbital (hepatic inducers) are accompanied by a slight increase of GGT, which is not worrisome, as long as its not associated with other LFT abnormalities (such as ALT abnormalities) or symptoms. Isolated direct hyperbilirubinemia is a mark of ATV treatment and, if not associated with any other laboratory abnormality or symptoms, doesnt need any intervention.

Full blood count

aemoglobin (Hb) is a protein in red blood cells and it also carries oxygen. H Mean cell volume (MCV) is a measure of the average red blood cell volume. A low Hb with low MCV (<70-80) may suggest iron deficiency anaemia (microcytic anaemia). A low Hb with high MCV (> 100 = macrocytic anaemia) may suggest specific types of vitamin deficiencies (folate, vitamin B12). A macrocytosis is also seen in patients on AZT, but this is not a concern as long as the Hb is not too low. This is a guide only, since chronic diseases such as HIV tend to cause a normocytic anaemia (low Hb with normal MCV) so interpretation may be difficult. Platelet count (PLT): platelets are the smallest blood cells and aid in the clotting of blood. They are formed in bone marrow. Trapping of platelets in liver disease could cause the spleen to be enlarged and the platelet count to decrease. Thats exactly what happens in case of severe liver disease (cirrhosis). People with a low platelet count (thrombocytopenia) could have the following conditions: untreated HIV or other viral infection, liver disease, or lymphoma.

Appendix 17

235

White blood cells (WBCs) or leucocytes are cells of the immune system that defend the body against infections and foreign materials.

Kidney tests
Creatinine is a breakdown product of muscle. It is filtered out of the blood into the urine by the kidney. Severe kidney damage could cause the creatinine levels in the blood to be high. However, this test is not suitable for detecting early kidney dysfunction. Creatinine clearance (CrCl), instead, is a useful test because it helps detect early kidney dysfunction. Creatinine levels in the blood and urine may be used to calculate the creatinine clearance. Many conditions (not only TDF) can cause reduction of CrCl, acutely (e.g. dehydration due to high fever, heavy diarrhoea, protracted vomiting...) or chronically (hypertension, diabetes, aging... and HIV itself!).Those conditions may warrant a particular treatment and follow-up. Its always better to check CrCl again after the resolution of an acute disease, if we think that the low result might have been affected by that: we might be able to avoid an unnecessary shift away from TDF! For severe renal failure, its advisable to reduce the dose of some of the ARVs (see Appendix 30 on page 266).

236

Appendix 17

Laboratory test normal values

Full Blood count and Platelets
Test White Cell Count Red Cell Count Haemoglobin Haematocrit MCV MCH MCHC Red Cell Distribution Width Platelets Normal result (reference range) 4.0 10.0 x 109/L 4.5 5.5 x 1012/L 10.5 17.0 g/dL 0.4 0.5 L/L (or 40 50%) 79.1 98.9 fL 27.0 32.0 pg 32.0 36.0 g/dL 11.6 14.0 % 137 373 x 109/L

Differential Count
Test Neutrophils Monocytes Lymphocytes Eosinophils Basophils Absolute CD4 Normal result (reference ranges) 1.5 7.5 x 109/L 0.18 0.80 x 109/L 1.0 4.0 x 109/L 0.00 0.45 x 109/L 0.00 0.20 x 109/L 500 2010 cells/L

Glucose values
Test Fasting glucose Normal result (reference range) 3.9-5.5 mmol/L

Appendix 17

237

Liver Function Tests

Test Bilirubin total Bilirubin conjugated Alkaline Phosphatase (ALP) Y-Glutamyl Transferase (GGT) Alanine Transaminase (ALT) Aspartate Transaminase (AST) Int Normalised Ratio (INR) Normal result (reference ranges) 0 21 mol/L 0 6 mol/L 40 120 IU/L 5-35 IU/L 5 40 IU/L 8 - 20 IU/L < 1.2 (in patients on oral anticoagulation for deep venous thrombosis, the target is 2.0 3.0).

Lipid Studies
Test (Need to be fasting bloods) Fasting Total Cholesterol LDL Cholesterol HDL Cholesterol (Males) (Females) Triglycerides <5.0 mmol/l <3.0 mmol/l >1.0 mmol/l >1.2 mmol/l <1.7 mmol/l Normal result (reference ranges)

Protein studies
Test CRP Quantitative ESR Normal result (reference ranges) <1.0 nmol/L 15 -20 mm/h

Kidney function
Test Potassium Chloride Urea Creatinine clearance Normal result (reference ranges) 3.3 5.3 mmol/L 99 113 mmol/L 2.6 7.0 mmol/L > 90 ml/minute (TDF contraindicated only if < 50 )

238

Appendix 18

Appendix 18: Safe preparation of

formula milk
South African PMTCT National Guidelines 1. Always use a marked cup or glass and a spoon to measure water and a scoop to measure formula powder. 2. Wash your hands before preparing a feed. 3. Bring the water to the boil and then let it cool. Keep it covered while it cools. 4. Measure the formula powder in to the marked cup or glass. Make the scoop level. Put one scoop for every 25 ml of water. 5. Add a small amount of cooled boiled water and stir. Fill the cup or glass to the mark with the water. Stir well. 6. Feed the baby using a cup. 7. Age Wash the utensils Weight Approximate (kg) amount of Previously boiled Number feed 2 2 3 5 6 7 8 Appropriate feeds/24hrs 8 x 50ml 8 x 50 ml 7 x 75 ml 6 x 125 ml 6 x 150 ml 6 x 175 ml 6 x 200 ml

of scoops/ number of

formula/24hrs water/feed Birth 2 weeks 6 weeks 10 weeks 14 weeks 3 3 4 5 6.5 400 ml 400 ml 600 ml 750 ml 900 ml 1050 ml 1200 ml 50 ml 50 ml 75 ml 125 ml 150 ml 175 ml 200 ml

4 months 7 5 months 8

Note: If formula different from the one given free of charge in SA, verify measurements.

Appendix 19

239

Appendix 19: Disclosure to

children
Disclosure is the process by which the child learns about his/her HIV/AIDS status. One can distinguish between partial disclosure (giving the child information about what is happening in his body without naming the virus and the disease), and total disclosure (telling the child he is infected with HIV and giving him/her all the information needed about HIV/AIDS). For all children < 12 years, it is usually recommended to go for progressive disclosure, starting with partial disclosure. Each child is unique so he/she will also be our guide. Importantly, however, one should make sure that full disclosure is reached before adolescence. Difficult reactions are often seen in adolescents when they find out their diagnosis late. For older children/adolescents, disclosure can also be particularly important to ensure adherence. Caretakers are often very hesitant to disclose to the child. Some of the common reasons (among many others) are: 1) belief that the child is too young to know 2) fear that the child cannot maintain a secret 3) the mother may feel ashamed to talk to the child about the transmission of the disease. There are many reasons why to tell children they are HIV positive. Some of these are: Child should hear about HIV from caregiver and not from other sources Honesty is important in child-caregiver relationship Children often know the truth before we expect or think they do Children often cope with the truth better than we anticipate Secrecy may be associated with increased behavioural problems Provide child with a sense of control over their lives Child should know why they go to the hospital and have blood taken regularly Its their right to know Protect others from infection Gives child permission to talk openly about HIV with caregivers.

Nurses, doctors, and counsellors have an important role to play in helping caretakers through the process of disclosure. This can take time! Example of a simple disclosure plan: Information about hygiene

240

Appendix 19

REMEMBER Start the disclosure process as early as

possible
t the latest when the child starts asking questions A The longer we wait, the bigger the risk of losing the childs trust The more the secret lasts, the more difficult it will be to break the silence Always achieve total disclosure before adolescence

Information about being sick Information about going to the doctor Information about the body Information about blood circulation Information about germs and getting sick Information about our defences (immune system) Information about immune system needing assistance from drugs Information about the specific virus the child has Naming the virus and the illness: HIV/AIDS Discuss with the child with whom the secret should be shared Information about CD4 count (and/or viral load if available) Information about transmission & non-transmission of HIV/AIDS Information about sexual relations and condoms use Total disclosure Partial disclosure

Reference: K. Bosteels and D. Goetghebuer; Patient support for HIV infected children; MSF September 2008.

Appendix 20

241

Appendix 20: Collecting a good

sputum sample
A good sputum specimen consists of recently discharged material from the bronchial tree, with minimum amounts of oral or nasal material. Satisfactory quality implies the presence of mucoid or mucopurulent material and is of greater significance than volume.

Procedure
1) Reassure the patient by explaining the reason for sputum collection. 2) Instruct the patient to rinse his/her mouth with water before producing the specimen. This will help to remove food or any contaminating bacteria in the mouth. 3) Give the patient a new sputum container 4) Instruct the patient to take two deep breaths, holding the breath for a few seconds after each inhalation and then exhaling slowly. Ask him/her to breathe in a third time and then forcefully blow the air out. Ask him/her to breathe in again and then cough. This should produce a specimen from deep in the lungs. 5) Ask the patient to hold the sputum container close to the lips and to spit into it gently after a productive cough. 6) Examine the quality of the sputum specimen. Quality ones to be kept are: urulent or muco-purulent, P Thick and mucoid, Fluid, with chunk dead tissue from a lesion in the lung

Thin, clear saliva or nasopharyngeal discharge is not sputum: a new specimen should be collected. 7) Examine the quantity of the sputum specimen. Quality ones to be kept are: 3-5 ml: good, < 3ml: encourage the patient to cough again until a satisfactory specimen is obtained. Remember that many patients cannot produce sputum from deep in the respiratory tract in a few minutes. Give him/her sufficient time to produce an expectoration, which s/he feels, is produced by a deep cough.

242

Appendix 20

8) Securely close the container, 9) If there is no expectoration, consider the container used and dispose of it in the appropriate manner. 10) Once the first specimen has been collected, give the 2nd container for the collection of the 2nd specimen. 11) Wash hands with soap and water. 12) Send the sample without delay to the laboratory, or store sample in a cool, dark place until transport available.

Appendix 21

243

Appendix 21: Building a DR TB

Treatment Regimen
Step 1
Use any available + One of these + One of these

Group 1: First-line oral Pyrazinamide Ethambutol

Group 2: Injectables Kanamycin Amikacin Capreomycin Streptomycin

Group 3: Quinolones Levofloxacin Moxifloxacin Gatifloxacin Ofloxacin

Step 2

Pick one or more of these

Add Group 4 drugs until you have 46 drugs likely to be effective

Group 4: Second-line oral bacteriostatic Cycloserine/Terizidone Ethionamide/Protionamide PAS

Step 3

Consider use of these Consider adding Group 5 drugs in consultation with an MDR-TB expert if there are not 46 drugs available in the above categories Group 5: Drugs of unclear efficacy Clofazimine Linezolid Amoxicillin/clavulanate Imipenem/cilastatin Clarithromycin High-dose isonaizid

244

Appendix 22

Appendix 22: DR TB Monitoring

(see monitoring table on page 247)
Clinical
Baseline Clinical and Investigations
epeat smear, culture and DST prior to starting DR treatment R Medical history and physical exam by Doctor Weight and BMI HIV screening and CD4 (if not already done) Chest x-ray Pregnancy test (child bearing age) Audiometry (baseline and monthly during the intensive phase of treatment) Potassium, Magnesium, Calcium Serum creatinine and creatinine clearance Full blood count ALT Fasting Blood Glucose (FBG) Vision test for colour vision if on Ethambutol (see Ishihara test in Appendix 23).

Intensive Phase Monitoring

mear and culture monthly, repeat DST if: S ulture remains positive at 4 months C Patient is clinically deteriorating If culture becomes positive after conversion (2 negative cultures one month apart) At the start of treatment, the patient should be assessed daily by the nurse for side effects to medication. Any concerns should be brought to the attention of the doctor immediately. The doctor should see the patient at least weekly during the first month and more often if any problems are developing. Once the patient is stable, the doctor can see the patient every 2 weeks. Patients weight check each week during the intensive phase. Periodic monitoring of ALT every 1-3 months in patients receiving Pyrazinamide, or patients at risk of or with symptoms of hepatitis.

Appendix 22

245

Creatinine clearance and potassium monthly during the injectable phase. Magnesium and Calcium 1 week after the start of treatment, then monthly during the intensive phase.* Audiometry monthly during the injectable phase. Repeat Ishihara test if any suspicion of change in colour vision Repeat chest x-ray at 6 months mear and culture done monthly, DST if patient is deteriorating clinically or S culture remains/or becomes positive again after conversion. Examination by doctor monthly unless there is a medical necessity to see the patient more often. Other medical team members see the patient between times and signal any concerns to the doctor.

Continuation Phase monitoring

Patients weight should be checked monthly. Chest x-ray repeated at 11 and 23 months ALT, FBC, creatinine if clinically indicated TSH levels every 6 months in patients on PAS and/or Ethionamide

Side Effects of Drugs

Second line TB drugs have many more adverse side effects than first-line anti TB drugs. Patients need to be informed of the potential side effects and when to notify the health care provider. Timely and aggressive management of all adverse effects is essential, whether they are minor (non life threatening) or major (life threatening). See Appendix 24 for management of side effects.

Adherence
Each patient who interrupts treatment should be traced immediately and the reasons for interruption should be explored. Every effort should be made to convince the patient to resume treatment. It is important to have a monitoring system in place to identify defaulters within 1-2 days of non adherence. If a patient has missed his/her clinic visit, a phone call and/or home visit should be undertaken to determine the reason(s) for non adherence.

* Currently in review

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Appendix 22

Counselling
Counselling of patients is of paramount importance and should be reinforced throughout treatment. DR TB treatment is very difficult to adhere to for many reasons. Some of these reasons are: sychological distress P Social problems Knowledge and belief regarding treatment purpose Separation from family/friends Side effects of medication Inconsistent immediate effect Trust in provider

Strategies to support patients with these numerous difficulties are many, but a basic package of support should include: atients should receive sufficient information and education about their disease P and treatment, given by nursing and medical staff to enable the patients to be responsible for their own treatment. It is very important that patients understand that if they do not adhere to their treatment, they are putting themselves at risk of developing resistant TB that is not treatable and they can pass this untreatable resistant TB to their families. Psychological support individually and/or in groups. DR TB support groups are now active at most clinics. Contact MSF adherence counsellor for more information. Intense medical support to treat side effects of drugs, addictions, other medical conditions, psychiatric disease and other pre-existing conditions or results of treatment. Social support, including accommodation, transport and other needs of the patients and their families; and to facilitate access to resources in the community. Some flexibility in treatment delivery to enable patients to stay adherent.

Monitoring Drug Resistant TB Patients

MONTH Smear Culture DST 1st line

DST 2nd line

CXR HIV screening CD4 (HIV +ve) Audiometry

Evaluation by PHC Doctor

Weight (BMI) Urinalysis Contraception Creatinine[1] Potassium[2]

Appendix 22

TSH[3] ALT[4] Hb[5] FBG[6] Pregnancy test Colour Vision

Baseline Intensive Phase Continuation Phase 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18-24 X X X X X X X X X X X X X X X X X X Monthly X X X X X X X X X X X X X X X X X X Monthly If at any time, culture becomes positive, or patient is clinically Repeat if client X X deteriorating, repeat 1st line DST and 2nd line DST (patient may now be (if culture clinically X resistant to more drugs) +ve) deteriorating X X X 18 & 24 X If previously -ve repeat at 6 months or if clinically indicated X X X 18 & 24 X Repeat as recommended by Audiologist or if clinically indicated (SA guidelines state monthly) Weekly during 1st month Every 2 X X X X X X X X X X X X X X Monthly weeks after X 1st month if patient is stable X Weekly X X X X X X X X X X X Monthly X X X X X X X X X X X X X X X X X X X Monthly X X X X X X X If on Capreomycin MONTHLY X in Intensive Phase X X X 18 & 24 X If clinically indicated X If clinically indicated X If clinically indicated X If clinically indicated X If clinically indicated

247

248

Appendix 22

1) While receiving an injectable (Kanamycin, Amikacin, Capreomycin, Streptomycin). Calculate creatinine clearance (see formula on page 196) 2) While receiving Capreomycin monthly in Intensive Phase and high risk patients 3) If patient taking PAS or Ethionamide will need baseline monitoring as indicated 4) If clinically indicated 5) Hb at baseline if clinically indicated 6) Fasting Blood Glucose if clinically indicated Recommendations contained in South African NDoH DR-TB Guidelines 2008

Appendix 23

249

Appendix 23: Ishihara Test for

Colour Blindness
What numbers do you see revealed in the patterns of dots below?

250

Appendix 23

Normal Colour Vision Left Top Middle Bottom 25 45 6 Right 29 56 8 Top

Red-Green Colour Blind Left 25 Spots Spots Middle Bottom Right Spots 56 Spots

Another interesting colour blindness test is below

The test to the left is simpler. The individual with normal colour vision will see a 5 revealed in the dot pattern. An individual with Red/Green (the most common) colour blindness will see a 2 revealed in the dots.

Appendix 24

251

Appendix 24: Management of

Adverse Effects of DR TB treatment
Common drug adverse reactions and management strategies
(Adapted from: World Health Organization. Guidelines for the Programmatic Management of Drug-resistant Tuberculosis (WHO/HTM/TB/2005.361), World Health Organization: Geneva, Switzerland, 2006). Adverse reaction Seizures Cs/Trd FQs Rule out other likely causes. Treat any suspected causes. Initiate anticonvulsant therapy (e.g. phenytoin 3-5 mg/kg/day; valproic acid 750-1250 mg/kg/ day; carbamazepine 600-1200 mg/day; phenobarbital 60-120 mg/kg/day). Increase pyridoxine to 300 mg daily. Lower dose of suspected agent. Discontinue suspected agent. Clinical evaluation generally sufficient unless suspicion high for infectious, malignant, vascular or metabolic cause. Anticonvulsant generally continued until DR-TB treatment completed or suspected agent discontinued. History of prior seizure disorder not a contraindication to the use of agents listed here if patients seizures are well-controlled and/or patient is receiving anticonvulsant therapy. Patients with history of prior seizures may be at increased risk for development of seizures during DR-TB therapy. Seizures not a permanent sequela of DR-TB treatment. Agent Management Comments

252

Appendix 24

Peripheral neuropathy

Cs/Trd S Km Am Eto/Pto E Cm

Increase pyridoxine to 300 mg daily. Begin exercise regimen, focusing on affected regions. Initiate therapy with tricyclic antidepressant drugs. Lower dose of suspected agent. Discontinue suspected agent . Initiate therapy with gabapentin (300mg QHS; increase by 600mg every 3-7 days; max dose 1200 TID).

Patients with co-morbid disease (e.g. diabetes, HIV, alcoholism) more likely to develop peripheral neuropathy, but these conditions are not contraindications to the use of the agents listed here. Neuropathy is generally not reversible, although only a minority (approximately 10%) of patients require continued intervention to keep symptoms controlled once DR-TB treatment completed.

Hearing loss

S Km Am Cm

Consider administration 5x or even 3x per week. Lower dose of suspected agent. Discontinue suspected agent. Initiate anti-psychotic drugs (e.g. risperidone 0.5-2 mg PO BID; haloperidol 1-5mg PO IV or IM repeated every hour as needed). Hold suspected agent for short period of time (1-4 weeks) while psychotic symptoms brought under control. Lower dose of suspected agent. Discontinue suspected agent.

Patients with prior exposure to aminoglycosides may have baseline hearing loss. Hearing loss is generally not reversible.

Psychosis

Cs/Trd FQs Eto/Pto

Some patients will need to continue anti-psychotic treatment throughout DRTB therapy. Prior history of psychiatric disease not a contraindication to the use of agents listed here but may increase the likelihood of development of psychotic symptoms. Psychotic symptoms generally reversible upon DR-TB treatment completion or discontinuation of offending agent.

Appendix 24

253

Depression

Cs/Trd FQs Cm Eto/Pto

Rule out side effects of concomitant medications, e.g. amoxycillinclavulanate, penicillin, benzodiazepines. Institute psychological therapy. Group or individual supportive counselling. Initiate anti-depressant drugs (e.g. amitriptyline, nortriptyline, fluoxetine, sertraline), but use with caution when history of convulsions. Increase pyridoxine to 300 mg daily. Consider anti-psychotics. Lower dose of suspected agent. Discontinue suspected agent.

Importance of socioeconomic conditions should not be underestimated as contributing factor to depression. Depression and depressive symptoms may fluctuate during therapy. History of prior depression is not a contraindication to the use of the agents listed here; however, these patients may be at increased risk for developing depression during DR-TB treatment.

Nausea and vomiting

Eto/Pto Cm E Z PAS

Rehydration Initiate anti-emetics 30 min prior to DR-TB drugs. Administer Eto in 3 separate doses. Administer Eto at night with short-acting benzodiazepine. Lower dose of suspected agent. Discontinue suspected agent.

Nausea and vomiting ubiquitous in early weeks of therapy and usually abate with supportive therapy. Electrolytes should be monitored and repleted if vomiting severe. Reversible upon discontinuation of suspected agent.

254

Appendix 24

Gastritis

PAS Eto/Pto E Z

Administer DR-TB medications with small amount of food. Avoid caffeine, cigarettes. Antacids (e.g. calcium carbonate, aluminium hydroxide, magnesiumhydroxide). H2-blockers (e.g. cimetidine, ranitidine), proton-pump inhibitors (e.g. omeprazole). Hold suspected agent(s) for short periods of time (e.g. 1-7 days). Lower dose of suspected agent. Discontinue suspected agent.

Severe gastritis possible, as manifest by hematemesis, melena or hematochezia. Dosing of antacids should be carefully timed so as to not interfere with the absorption of DR-TB drugs. Take fluoroquinolones at least 3 hours apart from antacids. Reversible upon discontinuation of suspected agent(s).

Hepatitis

Z FQs Eto/Pto PAS Cm E

Stop therapy. Rule out other potential causes of hepatitis. Re-introduce drugs individually while monitoring liver function, with most likely agent introduced first. Monitor liver function every 1-2 months.

History of prior hepatitis should be carefully analyzed to determine most likely causative agent(s); these should be avoided in future regimens. Generally reversible upon discontinuation of suspected agent.

Nephrotoxicity and renal failure

S Km Am Cm

Follow serum urea and creatinine, treat symptoms. Reduce dose of medication according to creatinine clearance. Discontinue suspected agent.

History of diabetes or renal disease not a contraindication to the use of the agents listed here, although patients with comorbidities may be at increased risk for developing renal failure. Renal impairment may be permanent.

Appendix 24

255

Optic neuritis Arthralgias

E Z Ofx

Stop agent Initiate therapy with non-steroidal antiinflammatory drugs. Initiate exercise regimen. Lower dose of suspected agent. Discontinue suspected agent. Symptoms of arthralgia generally diminish over time, even without intervention. Uric acid levels may be elevated in some patients but are of little therapeutic relevance and anti-gout therapy (e.g. allopurinol, colchicine) is of no proven benefit in these patients. Hypokalemia can occur without clinical signs and symptoms and may be lifethreatening.

Electrolyte disturbances (hypokalemia, hypomagnesaemia)

Cm Ka Am S

Replete potassium orally or IV. Treat associated vomiting or diarrhoea. Check magnesium levels if potassium levels do not improve Discontinue arrhythmagenic medications (e.g. digoxin, amitriptyline, cisapride, haloperidol). Discontinue aminoglycosides if severe.

The management of adverse effects often requires the use of ancillary medications to eliminate or lessen the event. Table 3 provides a list of indications and commonly used medications for the management of adverse reactions to second-line antituberculosis drugs.

256

Appendix 24

Commonly used ancillary medications

(Adapted from: World Health Organization. Guidelines for the Programmatic Management of Drug-resistant Tuberculosis (WHO/HTM/TB/2005.361), World Health Organization: Geneva, Switzerland, 2006). Indication Nausea, vomiting, upset stomach Heartburn, acid indigestion, sour stomach, ulcer Drug Metoclopramide, dimenhydrinate, prochlorperazine, promethazine, bismuth subsalicylate H2-blockers (ranitidine, cimetidine, famotidine, etc.), proton pump inhibitors (omeprazole, lansoprazole, etc.) Avoid antacids because they can decrease absorption of fluoroquinolones Fluconazole, clotrimazole lozenges Loperamide Selective serotonin reuptake inhibitors (fluoxetine, sertraline), tricyclic antidepressants (amitriptyline) Lorazepam, diazepam, clonazepam Dimenhydrinate Haloperidol, thorazine, risperidone (consider benzotropine or biperiden to prevent extrapyramidal side effects) Phenytoin, carbamazepine, valproic acid, phenobarbital Pyridoxine (vitamin B6 ) Amitriptyline Meclizine, dimenhydrinate, prochlorperazine, promethazine Ibuprofen, paracetamol, codeine Hydrocortisone cream, calamine, caladryl lotions Antihistamines (diphenhydramine, chlorpheniramine, dimenhydrinate), corticosteroids (prednisone, dexamethasone) Inhaled beta-agonists (albuterol, etc.), inhaled corticosteroids (beclomethasone, etc.), oral steroids (prednisone), injectable steroids (dexamethasone, methylprednisolone) Levo-thyroxine Potassium and magnesium replacement

Oral candidiasis (non-AIDS patient) Diarrhoea Depression Severe anxiety Insomnia Psychosis

Seizures Prophylaxis of neurological complications of cycloserine Peripheral neuropathy Vestibular symptoms Musculoskeletal pain, arthralgia, headaches Cutaneous reactions, itching Systemic hypersensitivity reactions Bronchospasm

Hypothyroidism Electrolyte wasting

Appendix 25

257

Appendix 25: Dosages of DR TB

Drugs
(Management of Drug Resistant TB in SA Policy Guidelines Draft 2008)

Intensive phase
Intensive phase: At least 6 months (at least six times per week)
Patient weight <33kg Drug Kanamycin Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Kanamycin Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Kanamycin Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Kanamycin Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Dosage 1520 mg/kg 1520 mg/kg 3040 mg/kg 800 mg 25 mg/kg 1520 mg/kg 1520 mg/kg 500750 mg 500 mg 10001750mg 800 mg 8001200 mg 500750 mg 500750 mg 1000 mg 750 mg 17502000 mg 800 mg 12001600 mg 750 mg 750 mg 1000 mg 750 - 1000 mg 2000 - 2500 mg 800 - 1000 mg 1600 - 2000 mg 1000 mg 750 1000 mg

33 - 50 kg

51 - 70 kg

>70 kg

258

Appendix 25

Other drug dosages:

PAS: Adults 8-12 grams per day divided 2-3 times per day (generally 4 grams every 12 hours); children 200-300mg/kg/day divided 2-4 times per day (maximum dose 10 grams in children) Capreomycin: 15mg/kg per day (normal renal function; max 1000 mg)

Continuation phase
Continuation phase: At least 18 months (at least six times
per week)
<33kg Patient weight Drug* Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Ethionamide Pyrazinamide Ofloxacin Ethambutol or Terizidone (Cycloserine) Dosage 15-20 mg/kg 30-40 mg/kg 800 mg 25 mg/kg 15-20 mg/kg 15-20 mg/kg 500 mg 1000-1750 mg 800 mg 800 - 1200 mg 500750 mg 500750 mg 750 mg 1750-2000 mg 800 mg 1200 - 1600 mg 750 mg 750 mg 750 - 1000 mg 2000-2500 mg 800 - 1000 mg 1600 - 2000 mg 1000 mg 750 1000 mg

33 - 50 kg

51 - 70 kg

>70 kg

* Ethambutol to be used if strain still susceptible vs. Terizidone (Cycloserine) to be used if strain resistant to Ethambutol Pyridoxine (B6) 150 mg to be given daily to patients on Terizidone (Cycloserine)

RDT = rapid diagnostic test for HIV Child > 12 months Do RDT and for children < 18months, confirm positive RDT with PCR Start ART as soon as possible if child < 18 months meets WHO criteria for Presumptive diagnosis of severe HIV disease Wean from breast milk unless age > 18 months and RDT + Clinically stage and perform CD4 test on the mother

Breastfeeding HIV-positive mother presenting with her child after 72 hours

BF = breastfeeding

Infant < 12 months

Do RDT for HIV in infant and if positive, perform PCR

Start ART as soon as possible if infant meets WHO criteria for Presumptive diagnosis of severe HIV disease

If not, start NVP for the infant and continue breast feeding

Clinically stage and perform CD4 test on the mother

Maternal CD4 > 200 and clinical stages 1, 2 Maternal CD4 > 200 and clinical stages 1, 2 RDT + (> 18 months) Or PCR + (< 18 months) RDT neg Or PCR neg

Maternal CD4 < 200 or stages 3, 4

Maternal CD4 < 200 or stages 3, 4 Start ART for the mother RDT + (> 18 months) Or PCR + (< 18 months) RDT neg Or PCR neg

Await PCR results if still pending RDT or PCR neg

Start ART for the mother

PCR +

RDT or PCR neg

PCR +

Appendix 26: PMTCT in late

presenters (I.e. after 72 hours of life)

Switch infant to ART Wean at 12 months Re-test child 6 weeks after BF cessation and at 18 months Start children on ART according to eligibility criteria (see Appendix 4) Continue BF if not already weaned

Continue breastfeeding

Continue infant NVP prophylaxis (until 1 week after BF stopped)

Switch infant to ART

Continue NVP until > 4 weeks of maternal ART

Re-test child 6 weeks after BF cessation and at 18 months Continue follow up of mother

Wean at 12 months if a nutritionally adequate diet can be provided

Continue breastfeeding

Start children on ART according to eligibility criteria (see Appendix 4) Continue BF if not already weaned

Re-test child 6 weeks after BF cessation and at 18 months Continue follow up of mother

Appendix 26

Re-test child 6 weeks after BF cessation and at 18 months

259

260

Appendix 27

Appendix 27: Common, serious

chest x-ray findings in PLWHA

Photo credit: Dr. G. Meintjes

Figure 1: This image shows a right-sided pleural effusion which is highly suggestive of tuberculosis (TB) in a person having cough, fever, night sweats, and/ or weight loss. If straw-coloured fluid is found during pleuracentesis (pleural tap), this helps to confirm the diagnosis. TB treatment should be initiated immediately.

Figure 2: This image demonstrates a miliary pattern in a section of the left lung. The hundreds of tiny seeds seen here represent hematogenous spread of TB. Treatment with TB medication should be initiated immediately.

Appendix 27

261

Figure 3: Enlarged lymph nodes are seen in the right mediastinum of this woman with severe immunodeficiency (CD4 count = 20 cells/L). Although her sputum was negative for acid-fast bacilli (AFB), she was started on TB treatment on the basis of her clinical condition and this x-ray result.

Photo credit: Dr. G. Meintjes

Figure 4: This woman presented with fever, cough, significant shortness of breath, and a low CD4 count. The x-ray shows a widespread interstitial infiltrate with reticulonodular markings that are more pronounced in the lower lobes. The presence of hypoxemia provided further evidence for Pneumocystis pneumonia (PCP). Treatment included high-dose CTX and steroids.

262

Appendix 28

Appendix 28: Common, serious

retinal findings in PLWHA
performed through dilated pupils! All patients with CD4 < 100 cells/L should have a retinal examination

Figure 1: Active CMV retinitis typically appears as dense retinal whitening with an irregular border having satellite lesions, and sometimes hemorrhage. It tends to follow vessels and as it spreads centrifugally, central clearing can be seen in larger lesions. Blindness is imminent in this case since the retinitis is encroaching on both the fovea and optic disk. CMV retinitis is the most common
Photo credit: Dr. Gary Holland

AIDS-related cause of blindness; much of this blindness could be prevented if all those with CD4 counts < 100 cells/L receive retinal screening to allow for early diagnosis and CMV-specific treatment.

Figure 2: The area of dense retinal whitening situated inferonasal to the optic disk is a result of primary toxoplasmosis. Since this retinal finding could also be due to syphilis, correlation with clinical condition and laboratory results is important.
Photo credit: Dr. David Heiden

Appendix 28

263

Figure 3: Tuberculosis usually affects the choroid through hematogenous spread. The four gray-yellow nodules seen here are choroidal tubercles. Since they are deep to the retina, their borders are indistinct; note that the retinal blood vessels can clearly be
Photo credit: Dr. Emmett Cunningham

seen in front of these lesions. There are usually < 5 in number, but may be up to 50. Choroidal tubercles can range from of a disc diameter to several disc diameters in size.

Figure 4: Papilledema with associated hemorrhage, which in this case was due to Cryptococcal meningitis.

Photo credit: Dr. Richard Imes

264

Appendix 29

Appendix 29: Fine needle

aspiration biopsy (FNAB)
A FNAB allows cellular material from lymph nodes to be examined for microscopic evidence of TB or other pathology (fungal infections, lymphoma, etc).

Equipment needed:
Gloves Povidone-iodine solution (or alcohol swab) Sterile gauze Sterile needle (23 gauge is best) 10 ml syringe Sterile water 2 microscope slides (frosted at one end) Spray fixative Pencil

Fine needle aspiration technique:

Label both microscope slides with patient identification and the date Disinfect the skin overlying the lymph node with the povidone-iodine solution (or alcohol swab) With the needle attached to the syringe, draw some sterile water into the syringe Immediately expel the water from the syringe (so that there is now a small coating of water inside the needle and syringe) Immobilizing the lymph node with one hand, insert the needle deep into the lymph node and pull back on the syringe plunger in order to create a vacuum (of about 2 ml) Without exiting the lymph node, withdraw and insert the needle several times at different angles in a back-and-forth motion, all the while maintaining constant suction, in order to allow cells from the lymph node to enter the bore of the needle Once material (or blood) appears in the needle hub, the aspiration should be stopped; the more cellular material aspirated, the better, since it improves the specificity and sensitivity of this diagnostic intervention

Appendix 29

265

Release the negative pressure before removing the needle from the lymph node. If not, the aspirated material will enter the barrel of syringe and be less available for introduction onto the microscope slides.

With the gauze, ask the patient to apply gentle pressure over the entry site

Slide preparation
It is important to prepare the microscope slides immediately after aspiration as follows: Detach the needle from the syringe Gently fill the syringe with air (while the needle is still detached) Reattach the needle to the syringe and quickly expel all of the air while the needle tip is touching close to the frosted end of one of the slides. By doing so, moist cellular material will be released onto the slide. Gently place the 2nd clean slide face down over the slide with the aspirate on it With the two slides now touching each other, move them in opposite directions in order to spread the cellular material across both slides simultaneously. Avoid pressing the slides together forcefully so as to avoid crushing the cells from the lymph node. Allow one slide to air dry Spray the other slide with fixative

Slide transport
The microscope slides must be well protected during transport to the laboratory.

266

Appendix 30

Appendix 30: Dose adjustment

of ARVs, CTX and other drugs in case of renal failure
Drug CTX-treatment CTX-prophylaxis Fluconazole Acyclovir DDI buffered tabs CrCl > 50 100% 100% 100% 400 mg TDS 400 mg OD CrCl 1050 50% 100% 50% 400 mg BID 200 mg OD CrCl < 10 refer 100% 50% 200 mg OD < 60 Kg 100 mg OD > 60 Kg 150 mg OD DDI coated tabs D4T 3TC TDF AZT NVP, EFV, PIs and ABC 400 mg OD 30 mg BID 300 mg OD or 150 BID 300 mg OD 300 mg BID 300 mg BID 125 mg OD 30 mg OD 150 mg OD DO NOT USE 15 mg OD 1/4 of 150 mg tab OD DO NOT USE 100 mg TDS

No need for dose reduction

Index

267

268

Index

Index of Contents
A Abacavir 205, 213 Abdominal pain 25, 30, 74, 75, 221, 222, 224 Acyclovir 47, 48, 51, 52, 60, 64, 65, 126, 131, 266 Adherence 34, 122, 163, 164, 166, 169, 194, 198, 202, 245 Adrenaline 225 Aluvia 71, 203, 206, 209, See also Lopinavir/ritonavir Amphotericin B 61, 116 Anaemia 174, 190, 192, 221, 234 Angular stomatitis 62 Antibody test Hepatitis B 75 HIV 151, 200, 201 Antiretroviral therapy (ART) Baseline blood tests 16, 196, 202, 219 Eligibility Adults 198 Children 200 Failure (virological) 163, 171, 210 First-line ARV regimens 163, 207 Adults 199 Children 211 Fast-track 17, 162, 194, 200 Monitoring 146, 164, 167, 219 Principles 162 Resistance 162-164, 228 Second-line ARV regimens 163 Adults 209 Children 211 Substitution of an individual ARV 163, 172, 229 Switching in event of failure 163, 166, 169, 170-171 Tail protection 228 Anxiety 122, 256 Aphthous ulcers 63 Atazanavir 203, 206, 210 AZT, See Zidovudine (AZT) B Bacterial folliculitis 40, 49 Bacterial meningitis 32, 114-115 Bacterial pneumonia 3, 80, 81, 92, 103105 Bactrim, See Cotrimoxazole (CTX) Bedsores 34, 56 Blisters 40, 50, 54, 126, 130, 225 Body mass index (BMI) 14, 15, 28, 165, 176, 199, 209

Index

269

Body surface area (BSA) 218 Breastfeeding 144, 146, 147, 149, 151, 157-159 C Carbamazepine 47, 187, 230, 251, 256 CD4 cell counts 3, 8, 165, 167 CD4 percentages 155, 171 Cerebral toxoplamosis 117-118 Cervical cancer 3, 134, 136 Chest x-ray findings in PLWHA 260-261 Chicken pox, See Varicella Chronic obstructive pulmonary disease (COPD) 80, 81 CMV, See Cytomegalovirus (CMV) Confusion 24, 31, 33, 34, 115, 123, 221 Contraception 17, 128, 138, 146, 196, 230

Cotrimoxazole (treatment dosages) Diarrhea 68, 70, 71, 72 PCP 80, 106-108 Toxoplasmosis 118 Cough 25, 80 Counseling 15-17, 150, 194, 246 Creatinine clearance (CrCl) 76, 178, 196, 235, 266 Cryptococcal meningitis 19, 34, 115-116, 263 Cryptosporidiosis 3, 68, 72 Cytomegalovirus (CMV) 16, 24, 34, 64, 72, 74, 118, 179 Retinitis 34, 262 D D4T, See Stavudine Dapsone 21, 106, 107 Dehydration 69, 70

Cotrimoxazole preventive therapy (CPT) Delirium 123 Desensitization 233 Dosing (adults) 21 Dosing (children) 156 Dose adjustment in case of renal failure 266 Eligibility criteria 21 Infants and children 108, 147, 151, 156 Primary prevention 19 Secondary prevention 19 Side effects 21, 225 Difficulty swallowing 24, 28, 60, 61, 64 Dementia 3, 118 Depression 30, 122, 230, 231, 253, 256 Developmental milestones 119, 154, 167 Diarrhea 25, 68, 256 Acute 69-71 Chronic 71-73, 190, 192 Didanosine (ddI) 205, 214, 266

270

Index

Disclosure 14, 152, 194, 202, 239 Dizziness 172, 174, 224 DNA PCR testing in infants 149, 150, 151, 201 DRTB, See Drug-resistant TB (DRTB) Drug interactions 180, 228, 230 Drug rash 54, See also Stevens-Johnson syndrome Drug-resistant TB (DRTB) 99-103, 243, 244-248, 251-256, 257-258 Drug sensitivity testing (DST) 100, 101 Dyspnoea 81, 105, 106 Dysuria 26, 126, 130 E Efavirenz (EFV) 206, 214 Eligibility ART (adults) 198 ART (children) 200 Cotrimoxazole preventive therapy 21 Emtricitabine (FTC) 203, 205 Encephalopathy 34, 118, 119, 168, 171 Exclusive feeding 144-147, 151, 157-159 Extra-pulmonary TB (EPTB) 29, 82, 84, 91, 191, 193 F Fast-track (for ART) 17, 162, 194, 200 Fever 25, 26, 201, 213, 221

Fine needle aspiration biopsy (FNAB) 35, 36, 84, 85, 86, 93, 264 First-line ARV regimens 163, 207 Adults 199 Children 211 Fluconazole 19, 45, 60, 61, 62, 64, 65, 116, 134, 206, 230, 256, 266 Fluoroquionolones 99, 254, 256 Focal signs (neurological) 27, 33, 117, 123 Folliculitis, See Bacterial folliculitis Formula feeding 144, 145, 147, 151, 157, 158, 238 G Genital ulcer syndrome 129, 130-131 Genital warts 40, 49, 135, 136, See also Human Papilloma Virus (HPV) Growth 153, 154, 171 H HAART, See Antiretroviral therapy (ART)

Head circumference 119, 153, 154 Headache 31, 33, 95 Hepatitis 175, 221, 224-225, 254 Hepatitis B virus (HBV) 75, 166, 197, 210 Herpes Simplex (HSV) 24, 47, 130 Herpes Zoster (Shingles) 50 High lactate, See Hyperlactatemia

Index

271

HIV Epidemiology 8 Life cycle 8, 165 Primary prevention 9 Transmission 9, 47, 128, 162, See also PMTCT Human papilloma virus (HPV) 49, 134136 Hyperglycemia 178 Hyperlactatemia 74, 175-177, 209, 227 Hypersensitivity reaction (HSR) 178, 213, 256 I Immune reconstitution inflammatory syndrome (IRIS) 51, 53, 94, 164, 171, 179 Immunization 151, 155 Impetigo 50 Infant feeding 157-159 Integration (TB-HIV) 83 IRIS, See Immune reconstitution inflammatory syndrome (IRIS) Isoniazid preventive therapy (IPT) 19, 20, 95-96 Isosporiasis 68, 72 Ivermectin 43, 44 K Kaletra 203, 206, See also Lopinavir/ ritonavir

Kaposi sarcoma (KS) 52, 109, 195 Karnofsky performance score 84, 85, 86, 232 Kidney dysfunction, See Renal failure L Lactic acidosis 74, 75, 164, 173, 175-177, 185, 209, 222, 224, 227-229 Lamivudine (3TC) 205, 213, 266 LIP, See Lymphoid interstitial pneumonia (LIP) Lipodystrophy 178, 222, 227 Lopinavir/ritonavir 90, 203, 206, 214 TB treatment 210 Lower abdominal pain 74, 127, 132-133 Lumbar puncture (LP) 31-34, 115-118 Lymphadenopathy 26, 35, 84-86, 91, 93, 131, 261, 264 Lymphoedema 53 Lymphoid interstitial pneumonia (LIP) 93, 108 Lymphoma 3, 25, 26, 35, 36, 74, 118, 235, 264 M Mantoux testing, See Tuberculin skin testing (TST) Mebendazole 153 Meningitis 32, 34, 114-117 Micronutrients 1, 4, 29

272

Index

Microsporidiosis 72 Molluscum contagiosum 40, 48, 192 N Nappy rash 46 Nausea 173, 221, 222, 253, 256 Nevirapine (NVP) 206 Children 215 Hepatitis 175 HIV-exposed baby 147-149, 151 PMTCT 144 Rash 173-174 TB treatment 90 Non-tuberculous mycobacterium (NTM) 3, 87, 191, 193 Nutrition 1, 4, 15, 29, 70, 94, 153, 195 O Oesophageal candidiasis 3, 24, 28, 60, 61, 64, 191, 193 Opportunistic infection (OI) 3 Oral candidiasis (thrush) 61-62, 190, 192 Oral hairy leukoplakia (OHL) 63, 190, 192 Oral health 61 P Pain management 34, 109, 184-186, 187 Pancreatitis 175, 226 Pap smear 16, 18, 136

Papular pruriginous eruption (PPE) 42, 190, 192 PCR testing in infants, See DNA PCR testing in infants Pelvic inflammatory disease (PID) 127, 132-133 Peripheral neuropathy (PN) 89, 112-114, 174-175, 223, 252 Physical examination 14, 15 Children 152-153 PMTCT ARV regimens 144 Late presenters 259 Pneumocystis pneumonia (PCP) 80, 105-108, 117, 191, 193 Post-exposure prophylaxis (PEP) 9, 138 Accidental exposure of HCW 10 Sexual assault 138-139, 140 Post-herpetic neuralgia 50, 51, 185 PPD 20, See also Tuberculin skin testing (TST) Pregnancy ARV regimen 208 Dapsone 21 Efavirenz 204, 206 Fluconazole 116 HIV 144-146 HIV viral load 169 Isoniazid (INH) 95

Index

273

Pap smear 136 Sexual assault 138, 140 STIs 127, 132 Streptomycin 88 Syphilis 137 Tuberculosis 90, 91 Presumptive diagnosis of severe HIV disease in infants 200-201 Prevention OIs, See Cotrimoxazole preventive therapy (CPT) and Dapsone Isoniazid, See Isoniazid preventive therapy (IPT) Progressive multifocal leukoencephalopathy (PML) 3, 34, 193 Protease inhibitors 9, 173, 178, 203 Pseudomonas 56, 103

HIV 4, 162, 163, 164, 177, 178, 209, 228 Gonorrhoea 129 Tuberculosis, See Drug-resistant TB (DRTB) Retinal examination 16, 32, 262 Rifampicin 230 Ritonavir super-boosting 92, 210, 212 S Scabies 40, 42, 43 Seborrheic dermatitis 46 Second-line ARV regimens 163 Adults 209 Children 211 Seizures 26, 32, 33, 34, 115, 117, 176, 251, 256 Sexual assault 137-139, 140, 150

Psoriasis 55 Sexually transmitted infections (STIs) 14, Psychosis 123, 224, 252, 256 Pyridoxine 89, 94, 95, 96, 112-114, 185, 251-253, 256, 258 Side effects R Ramsey Hunt Syndrome 51 Rash 24, 40-56 ARV-related 173, 221, 225 Renal failure 88, 100, 178, 197, 199, 204, 222, 229, 235, 254, 266 Resistance ARVs 163, 164, 168, 171-178, 221222, 223-229 Cotrimoxazole 21, 233 DRTB drugs 245, 251-256 Sputum collection 93, 241-242 Staging (clinical) of HIV infection 15, 155 Adults 190-191 35, 128-137 Shingles, See Herpes Zoster

274

Index

Children 192-193 Stavudine (d4T) 90, 205, 209, 215, 266 Stevens-Johnson syndrome 24, 54, 172, 174 Stunting 153 Swollen testes 126, 130 Syndromic STI management 126-128, 130-132 Syphilis 16, 32, 34, 35, 40, 126, 130, 131, 137, 144, 262 T Tail protection 144, 177, 224, 226, 227, 228 TB, See Tuberculosis (TB) Tenofovir (TDF) 88, 205, 228, 235, 266 Thrush, See Oral candidiasis and Vulvovaginal candidiasis Tinea corporis 44-45 Tinea pedis 44 Toxoplasmosis 19, 21, 117-118, 191, 193, 262, See also Cerebral toxoplasmosis U

Infection control 97 Meningitis 95, 117 Pulmonary 80, 81, 83, 86, 91, 92, 96, 155 Prevention 95 Screening 14, 25, 144 Screening in children 30, 92, 96, 98 Smear-negative algorithm 84, 86

Urethral discharge 126, 130, V Vaginal discharge 127, 129, 131-132, 134 Varicella (chicken pox) 50, 52 Viral load 18, 149, 151, 166, 167, 169, 219 Vomiting 173, 221, 222, 224, 252, 256 Vulvo-vaginal candidiasis 133-134 W Warts, See Genital warts Wasting syndrome 3, 28, 29, 191 Weight Loss 14, 28, 30, 221, 222

Tuberculin skin testing (TST) 20, 95, 98, 102, 103 Tuberculosis (TB) ART 91, 195, 210, 212 Co-infection with HIV 199 Contact tracing 102 Drug-resistant (DRTB) 99-103, 243, 244-248, 251-256, 257-258 Window period (for HIV antibody testing) 149, 151 X Xerosis 40, 41 Z Zidovudine (AZT) 204, 214, 266