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    HIV-lecture for C1

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    HIV-lecture for C1

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    dursaoro

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    © All Rights Reserved
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    Pediatric HIV

    Hamze wabari
    MD
    Content of lecture
    Introduction
    Epidemiology of HIV/AIDS
    Pathogenesis of HIV/AIDS
    HIV life cycle
    Natural history
    Diagnosis of HIV
    Staging of HIV
    Principles of treatment
    Introduction
    AIDS first recognized 1981

    HIV RNA retrovirus discovered 1983

    2nd leading cause of disease burden worldwide

    Leading cause of death in Africa

    Approx. 31-44 million people living with HIV


    worldwide
    The Global Situation of Pediatrics HIV
    Infection
     HIV infection is a major cause of infant and childhood

    mortality and morbidity in Africa

    Each day in 2020 approximately 850 children become

    infected with HIV and 330 children died from AIDS ,

    mostly because of inadequate access to HIV

    prevention ,care and treatment services


    Pediatrics HIV infection in Ethiopia
    The first HIV exposed newborn in Ethiopia was
    identified in 1986
     The office’s projection for 2021 shows that at least
    622,000 people live with the virus while the viruses cause
    12,000 death annually
    Currently the office estimated 86% of Ethiopian
    living with HIV know their HIV positive status and
    94% of them are currently receiving ART
     92% of pregnant women living with HIV accessed
    the medicine , preventing 3700 new HIV infection
    among newborn
    Epidemiology
    Mode of HIV transmission
    MTCT
    Sexual transmission among adolescents
    Sexual abuse
    Transfusion of infected blood or blood product
    Un sterile injection 2.5%
    95%HIV infected infant acquired from their mother
    - During pregnancy
    - During delivery
    - Postnatal trough breast feeding
    Cont epi
    Risk of contracting infection dependent on
    • Viral load
    • Integrity of the exposed site
    • Type of body fluid
    • Volume of body fluid
    Risk after a single exposure
    • >90% blood or blood products
    • 14% vertical
    • 0.5-1% injection drug use
    • 0.2-0.5% genital mucous membrane
    • <0.1% non-genital mucous membrane
    Time of transmission Transmission Rate(%)

    During pregnancy 5-10


    During labor and delivery 10-20
    During breast feeding 5-20
    Overall without breast feeding 15-30

    Overall with breast feeding for 25-35


    6mon
    Overall with breast feeding for 30-45
    18-24mon
    Life cycle
    Fusion  Entry  Transcription Integration 
    Cleavage  Assembly  Budding
    Pathogenesis
    There are 2 type HIV
    HIV 1
    HIV 2 found in west Africa
    - less pathogenic
    - make no contribution to pediatrics AIDS
    HIV 1 has many subtypes
    - A and D east and central Africa
    - C south Africa ,more virulent ,fast disease progression
    high rate of MTCT
    Cont pat
    Anatomy of the HIV Virus
    Gp120 Envelope Protein
    Gp41 Envelope Protein
    P17 matrix protein
    P24 Capsule Protein

    Reverse Transcriptase

    The Lipid Membrane


    Cont pat
    Glycoproteins (gp 120, gp41)

    2 copies of ssRNA, viral enzymes

    Attachment with gp 120 to CD4 receptor

    Fusion mediated by gp 41

    Inside cell RNA transcribed to DNA by RT

    DNA incorporated into cell genome

    DNA is copied and translated to viral enzymes, proteases

    New infectious virus buds from host cell to repeat process


    Effect on immune system
    CD4 cell depletion and dysfunction

    Lymphoid tissue distraction

    CD8 cell dysfunction

    B cell abnormality

    Thymes dysfunction

    Auto immune dysfunction


    Cont….
    Gradual reduction in number of circulating CD4 cells
    inversely correlated with the viral load
    Any depletion in numbers of CD4 cells renders the body
    susceptible to opportunistic infections
    Lymphatic tissue (spleen, lymph nodes,
    tonsils/adenoids) main reservoir of HIV
    Natural history
    With no intervention the majority of prenatally infected
    children in Africa develop HIV related symptom by

    6 months of age
    Children prenatally infected has 3 category

    Category 1 rapid progresser die with in 1 year(25-35%)

    Category 2 die with in 3-5 years (50-60%)

    Category 3 who live beyond 8 years (5-25%)


    Primary Infection

     70-80% symptomatic, 3-12 weeks after exposure

     Fever, rash, cervical lymphadenopathy, aseptic


    meningitis, encephalitis, myelitis, polyneuritis
     Surge in viral RNA copies to >1 million

     Fall in CD4 count to 300-400

     Recovery in 7-14 days


    Sero conversion
     3-12 weeks, median 8 weeks

     Level of viral load post seroconversion correlates with


    risk of progression of disease
     Differential for this syndrome: EBV, CMV, Strep
    pharyngitis, toxoplasmosis, secondary syphilis
    Asymptomatic phase

     Remain well with no evidence of HIV disease


    except for generalized lymphadenopathy
     Fall of CD4 count by about 50-150 cells per year
    Symptomatic phase

    • Mild impairment of immune system

    • Chronic weight loss

    • Fever

    • Diarrhea

    • Mild candida infections

    • Recurrent herpes infections


    AIDS
    • CD4 <200
    • Pneumocystis pneumonia
    • Esophageal Candidiasis
    • Mucocutaneous herpes simplex
    • Miliary/extrapulmonary TB
    • Cryptosporidium
    • HIV-associated wasting
    • Microsporidium
    • Peripheral neuropathy
    AIDS

    • CD4<50
    • CMV retinitis, gastroenteritis

    • Disseminated Mycobacterium avium complex


    DIAGNOSIS

    • Clinical

    • Laboratory

    antibody

    virologic
    Dx using IMCI algorithm
    The IMCI guidelines in most countries now include symptoms
    suggestive of HIV.
    a child is classified as symptomatic HIV if any four of the
    following are identified.
    • Recurrent pneumonia
    • Oral thrush
    • Present or past ear discharge
    • Persistent diarrhea
    • Very low weight
    • Enlarged lymph nodes
    • Parotid enlargement
    Diagnosis
    Antibody test: ELISA, rapid test and western blot
    Virologic test :HIV DNA PCR assays,

    RNA assays (viral load, HIV immune complex-


    dissociated p24 antigen assays, and HIV peripheral
    blood mononuclear viral culture.
    WHO CLINICAL STAGING

    STAGE 1

     Asymptomatic

     Persistent generalised lymphadenopathy (PGL)


    STAGE 2
    • Unexplained persistent hepatosplenomegaly
    • Extensive wart virus infection; facial, more than 5% of body area
    or disfiguring
    • Papular pruritic eruptions
    • Fungal nail infections
    • Lineal gingival erythema
    • Extensive HPV or molluscum contagiosum (>5% of body area/face)
    • Recurrent oral ulcerations (>2 episodes/6 mos )
    • Unexplained persistent parotid enlargement
    • Herpes zoster
    • Recurrent or chronic upper respiratory infection (URI): otitis
    • media, otorrhea, sinusitis, tonsillitis (>2 episodes/6 mos )
    STAGE 3
    • Unexplained moderate malnutrition (-2 SD or Z score) not
    adequately responding to standard therapy
    •Unexplained persistent diarrhoea (≥14 days)
    •Unexplained persistent fever (intermittent or constant, >1 mo)
    •Persistent oral candidasis (outside 6–8 weeks of life)
    •Oral hairy leukoplakia
    • Lymphnode TB
    • Pulmonary tuberculosis
    • Severe recurrent presumed bacterial pneumonia (current
    episode plus)
    •Chronic HIV-associated lung disease including bronchiectasis
    •Unexplained anemia (<8 gm/dL), neutropenia (<1,000/mm3 ),
    or
    thrombocytopenia (<50,000/mm3) for >1 mo.
    STAGE 4
    For a symptomatic HIV-antibody positive infant age <18 mos,
    •make a presumptive diagnosis of severe HIV disease
    (clinicalStage 4) when:
    •a) Two or more of the following are present:
    Oral candidiasis/thrush
     Severe pneumonia
     Sepsis
    •or
    •b) Diagnosis of any AIDS-indicator condition(s) can be made
    •Other supporting evidence: recent HIV-related maternal death or
    •advanced HIV disease in the mother; and/or CD4 <20%
    •Presumptive diagnosis of Stage 4 disease in HIV-antibody
    positive
    infants <18 mos requires confirmation with HIV virologic tests
    when possible, or by antibody tests after age 18 mos.
    STAGE 4
    • Unexplained severe wasting or severe malnutrition (-3 SD, as
    defined by WHO IMCI guidelines) not responding to standard
    therapy
    • Pneumocystis pneumonia
    • Recurrent severe presumed bacterial infections; e.g. empyema,
    •pyomyositis, bone or joint infection, meningitis but excluding
    pneumonia (current episodes plus ≥1 in previous 6 months)
    • Chronic orolabial, cutaneous or visceral (any site) HSV infection
    (lasting >1 mo)
    • Extrapulmonary tuberculosis
    • Kaposi’s sarcoma
    • Esophageal candidiasis (or candida of the trachea, bronchi or
    lungs)
    • CNS toxoplasmosis
    • Extrapulmonary Cryptococcosis, including meningitis

    • Any disseminated fungal infection

    • Cryptosporidiosis or isosporiasis (with diarrhoea >1 mo)

    • CMV retinitis or infection affecting another organ, with onset at


    age >1 month

    • Disseminated mycobacterial disease other than tuberculosis

    • Acquired HIV-associated rectal fistula

    • Cerebral or B cell non-Hodgkins lymphoma

    • Progressive multifocal leukoencephalopathy (PML)

    • HIV encephalopathy
    Skin and Oral disease
    • Seborrheic dermatitis
    • Xeroderma
    • Itchy folliculitis
    • Scabies
    • Tinea
    • Herpes zoster
    • Papillomavirus
    • Oral and vaginal candidiasis
    • Oral hairy leukoplakia
    • Aphthous ulcers
    • Herpes simplex
    • Gingivitis
    • Kaposi’s sarcoma
    • Molluscum contagiosum
    • Bacillary angiomatosis
    GI disease
    • Esophageal candidiasis
    • Large bowel disease (bloody diarrhea)
    • C. diff
    • CMV
    • Small bowel disease (watery diarrhea)
    • Cryptosporidium
    • Microsporidium
    • Giardia
    • MAC
    • CMV
    Pulmonary Disease

    • Pneumocystis pneumonia
    • Bacterial pneumonia
    • LIP
    • Nocardia
    Pneumocystis pneumonia(pcp)
    Most common AIDS presenting illness

    Reactivation of infection (original airborne transmission,


    asymptomatic, early age)
    Inversely correlated with CD4 count

    40% of patients with CD4 <100 and not prophalaxed will


    have pneumonia annually
    Prophalaxis started at CD4 <200, trimethoprim/sulfa,
    dapsone, atovaquone, pentamidine
    Nervous system disease
    • Toxoplasma

    • Cryptococcosis

    • PML

    • CMV retinitis

    • Developmental regression

    • Peripheral neuropathy
    Pre-Treatment Assessment
    The following evaluations should be part of the pre-
    treatment assessment:
     Complete clinical assessment
     Neurodevelopmental assessment
     Weight, length/height, and head circumference
     Complete blood count (CBC)
     Alanine aminotransferase (ALT)
     Chest radiograph
     CD4 count
     Viral load
    Ten-Point Package for Comprehensive Pediatric AIDS Care
    1. Confirm HIV status as early as possible.
    2. Monitor the child’s growth and development.
    3. Ensure that immunizations are started and completed
    4. Provide prophylaxis for opportunistic infections (PCP and TB)
    5. Actively look for and treat infections early.
    6. Counsel the mother and family on:
    7. Conduct disease staging for the infected child.
    8. Offer ARV treatment for the infected child
    9. Provide psychosocial support to the infected child and mother.
    10. Refer the infected child for higher levels of specialized care if
    necessary, or for other social- or community-based support
    programs
    Antiretroviral

    Nucleoside reverse transcriptase inhibitors

    Non-nucleoside reverse transcriptase inhibitors

    Protease inhibitors

    Fusion inhibitors

    R5/X4 inhibitors
    NRTIs
    • ddC
    • ddI
    • 3TC
    • ZDV
    • d4T
    • Abacavir
    • FTC
    NNRTIs
    • Nevirapine
    • Efavirenz
    • Delavirdine
    PIs
    • Indinavir
    • Saquinavir
    • Ritonavir
    • Nelfinavir
    • Lopinavir/ritonavir
    • Amprenavir
    • Fosamprenavir
    • Tipranavir
    • Atazanavir
    •
    Side effects
    NRTIs: mitochondrial dysfunction
    • ddC, ddI, d4T: neuropathy
    • d4T, ddI: hepatic steatosis, lactic acidosis
    • ddI: pancreatitis
    • ZDV: anemia
    • d4T: fat atrophy
    • Abacavir: hypersensitivity reaction
    • Tenofovir: renal failure
    • NNRTIs: rash, liver toxicity
    • PIs: fat redistribution, insulin resistance, hyperlipidemia
    • Indiavir: renal stones
    • Nelfinavir: diarrhea
    Monitoring and Follow-Up
    Clinical monitoring
    frequency of visit-2wk,monthly for the 1st
    3months,then every3-6months
    At each visit:
    Plot physical growth (weight, length/height, and head
    circumference).
     Determine physical condition of the child.
     Address ongoing medical problems, including skin and
    dental problems and organ-specific complications of HIV
    infection.
     Treat intercurrent infections, if present.
     Check the doses of the drugs.
     Monitor neurodevelopmental progress at 12-month
    intervals
    Laboratory Monitoring
     Repeat the CD4 count and % and viral load (where
    available) at 6-month intervals.
     Repeat CBC and ALT after 1 month of treatment; if
    normal, repeat these tests at 6-month intervals
    If protease inhibitors are used, test fasting lipid profiles
    (cholesterol and triglycerides) at baseline and then
    annually
     PCP prophylaxis may be discontinued when the CD4 is
    consistently >20%.
    Adherence monitoring
    Prevention
    A four-pronged approach has been suggested for PMTCT of HIV

    Prong 1: Primary Prevention of HIV Infection

    Prong 2: Preventing Unintended Pregnancy Among HIV-


    Infected Women

    Prong 3: Preventing Mother-to-Child HIV Transmission.

    prong 4: Antiretroviral Therapy for PMTCT


    Prevention
    THANK YOU!!!

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