VIH
VIH
VIH
MAJOR ARTICLE
Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a near
expected life span, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing em-
phasis on maintaining health throughout the life span. To receive optimal medical care and achieve desired outcomes, persons with HIV
must be consistently engaged in care and able to access uninterrupted treatment, including ART. Comprehensive evidence-based HIV
primary care guidance is, therefore, more important than ever. Creating a patient-centered, stigma-free care environment is essential for
care engagement. Barriers to care must be decreased at the societal, health system, clinic, and individual levels. As the population ages and
noncommunicable diseases arise, providing comprehensive healthcare for persons with HIV becomes increasingly complex, including
management of multiple comorbidities and the associated challenges of polypharmacy, while not neglecting HIV-related health con-
cerns. Clinicians must address issues specific to persons of childbearing potential, including care during preconception and pregnancy,
and to children, adolescents, and transgender and gender-diverse individuals. This guidance from an expert panel of the HIV Medicine
Association of the Infectious Diseases Society of America updates previous 2013 primary care guidelines.
Keywords. HIV primary care; HIV care engagement; HIV monitoring; HIV comorbidities; sexually transmitted infections.
Although substantial inequities exist by region and popula- must be an overarching priority of HIV primary care. Ensuring
tion, with continuous engagement in high-quality human im- stigma-free, culturally appropriate, and patient-centered care
munodeficiency virus (HIV) care and uninterrupted access experiences is essential to maximize care engagement, treat-
to antiretroviral therapy (ART), people with HIV now have ment adherence, and viral suppression. While ART has be-
the possibility of an expected life span that approaches that come more potent, less toxic, and simpler, other aspects of
of persons not living with HIV, free of opportunistic diseases HIV care have become increasingly complex as people with
and without horizontal transmission to partners or vertical HIV live longer and experience increased comorbidities
transmission to infants [1–4]. Ending the HIV epidemic, across the life span, requiring additional attention to issues
however, has proven challenging in the United States, with associated with aging with HIV [6–10]. Recommendations
only 59.8% of those aware of their HIV diagnosis achieving that are affected by age are noted throughout this guidance.
viral suppression, and even lower rates among African- Noncommunicable diseases, including metabolic compli-
Americans, Hispanic/Latinos, transgender women, persons cations, require guidance for prevention and management,
aged 13–24 years, persons who inject drugs (PWID), and particularly as the population ages. Persons of childbearing
those who live in the South [5]. Identifying and overcoming potential, children, adolescents, and transgender and gender-
barriers to care engagement and continuous ART, therefore, diverse individuals experience unique clinical challenges. As
ever-increasing numbers of people are living with HIV and
require both HIV-specific and primary medical care, the need
Received 8 September 2020; editorial decision 9 September 2020; accepted 11 September
2020; published online 6 November 2020.
for updated recommendations necessitated this update to the
a
Co-chaired the HIV Primary Care Guidance Panel. 2013 HIV Primary Care Guidelines from the HIV Medicine
Correspondence: M. A. Horberg, Kaiser Permanente Mid-Atlantic Permanente Medical
Association (HIVMA) of the Infectious Diseases Society of
Group and Care Management Institute, 2101 East Jefferson Street, 3 East, Rockville, MD 20852
(michael.horberg@kp.org). America (IDSA) [11]. “People First” language that places
Clinical Infectious Diseases® 2021;73(11):e3572–605 the person before the disease is used in this document to ac-
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society
knowledge the dignity of people with HIV, and gender-neu-
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/ciaa1391 tral language is used, where appropriate.
disclosure process. Work and educational histories should be Section VIII for further discussion of transgender and gender-
discussed, including whether these have been affected by the diverse health.
diagnosis of HIV. Other pertinent information includes insur-
ance issues, financial status, marital and family status, and plans Allergies and Medications
for having children. A discussion of allergies and intolerances should include ques-
It is critical to obtain a sexual history in an open, nonjudg- tions about hypersensitivity reactions to antibiotics and ART.
mental manner, asking about past and current practices [69]. Clinicians should ask about all current medications, including
Counseling and education should focus on attaining viral sup- dietary or herbal supplements, some of which have been shown
pression for optimal personal health and elimination of HIV to interact with ART. All prior ART regimens, including years
transmission to sexual partners (including education that Und of use, prior side effects, and reasons for switching, should be
etectable = Untransmittable), and risk reduction for other sex- recorded. It is also important to assess prior adherence to medi-
ually transmitted pathogens. Clinicians should ask about part- cations and document viral loads while on each regimen.
ners, sexual practices (including all exposure sites, condom and
contraceptive use), past sexually transmitted infections (STIs), Review of Systems
HIV status of partner(s), and whether the patient has informed The review of systems should be comprehensive and include
their partner(s) of their HIV status. Laws vary from state to questioning about common HIV-related symptoms (see Table 3).
state regarding the obligation of healthcare providers to notify Patients should be questioned about how their current weight
sex partners, and clinicians should be aware of laws in their own compares with their baseline, along with a dietary assessment.
jurisdiction. All clinicians should familiarize themselves with Depression is common among people with HIV, especially
basic discussions about gender identity, including communi- women, and the review of systems should include questions
cation about appropriate pronouns, and fundamentals of care that focus on changes in mood, libido, sleeping patterns, appe-
for transgender and gender-diverse individuals [70]. Please see tite, concentration, and memory. As part of the initial evaluation
Comorbidities: current or past chronic medical conditions that might affect the choice of therapy or response to therapy
• Prior and present gastrointestinal disease
• Liver disease, including viral hepatitis
• Cardiovascular disease and risk factors, including hyperlipidemia, hypertension, diabetes mellitus, smoking
• Osteopenia or osteoporosis
• Kidney disease
• History of receipt of blood products, organ transplant, or tattoos
Other past medical conditions that may have implications for persons with HIV
• History of chicken pox or shingles, measles
• Mycobacterium tuberculosis illness, exposure, treatment; prior testing or treatment for latent tuberculosis
• STIs, including syphilis, chlamydia, gonorrhea, herpes simplex, trichomoniasis, chancroid, HPV
• Abnormal anal cytology; past anorectal disease including warts, fissures
Gynecologic and obstetric history
• Cancer
Social history
• Race and ethnicity
• Gender identity and sexual orientation; pronouns
• Patient birthplace, residence, and travel history
• Employment history
• Incarceration history
• Education history
• Financial support
• Children: ages, plans for having children in the future; HIV status of children
• Pets
• Diet and exercise
• Sexual history: types of activity including partners and practices; sexual exposure sites; STI prevention including condom use; past STIs;
and at periodic intervals thereafter, providers should assess the (eg, dorsocervical fat pad, gynecomastia, or visceral abdominal
presence of depression, post-traumatic stress disorder, and fat accumulation) and/or lipoatrophy (eg, loss of subcutaneous
sexual or physical abuse, including domestic violence, by means fat in the face, extremities, or buttocks). All adult patients with
of direct questions or validated screening tools (Patient Health advanced HIV disease (CD4 cell count <50 cells/µL) as well as
Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder infants and young children with profound immunodeficiency
2-item [GAD-2]) [71, 72]. Persons with HIV have high rates of should be referred to an ophthalmologist for a dilated
adult sexual and physical abuse and of childhood sexual abuse. funduscopic examination. Though persistent generalized lym-
phadenopathy is common among untreated persons with HIV,
Physical Examination it does not correlate with prognosis or disease progression.
A complete physical examination should be performed at the However, focal or rapidly progressive lymphadenopathy may
initial encounter or as soon afterward as possible. In addition require further evaluation, including biopsy. Additionally, if
to recording all vital signs (including height and weight), head lymphadenopathy does not quickly resolve with initiation of
circumference should be measured in children aged <3 years ART, diagnostic studies should be pursued. Neurology and/or
and plotted against standard growth curves. Furthermore, de- neuropsychology referral for assessment of neurocognitive dis-
velopmental assessment is important in infants and children. orders, dementia, and focal neuropathies may be indicated [73,
Older persons should be assessed for frailty. For all patients, the 74]. Cervical motion and uterine or adnexal tenderness on bi-
overall body habitus should be assessed, looking for evidence of manual pelvic examination suggest pelvic inflammatory disease
wasting, obesity, or, particularly in patients who have received and should prompt STI testing. An anorectal examination is im-
older ART regimens, evidence of drug-related lipohypertrophy portant to evaluate for anal warts, other STIs, and anal cancer,
A complete review of systems with special attention to the areas listed A complete physical examination should be performed, with special attention
below: to the following areas:
• General: unexplained weight loss or gain, night sweats, fever, changes in • Vital signs: including height and weight
body habitus
• Skin: discoloration, rash, ulcers, or lesions • General: including body habitus, evidence of obesity, wasting, lipodystrophy,
assessment of frailty, and ambulatory ability
• Lymph nodes: localized or generalized enlargement of lymph nodes • Skin: seborrheic dermatitis, ecchymoses, purpura, petechiae, Kaposi
sarcoma, herpes simplex or zoster, psoriasis, molluscum contagiosum,
onychomycosis, folliculitis, condylomata, cutaneous fungal infections,
acanthosis
• Eyes: vision change or loss • Lymph nodes: generalized or localized lymphadenopathy
• Mouth: gum disease, ulcers, oral lesions, or pain • Eyes: retinal exudates or cotton wool spots, hemorrhages, pallor, icterus
• Cardiopulmonary: chest pain, palpitations, wheezing, dyspnea, orthopnea • Cardiovascular: heart exam, peripheral pulses, presence/absence of edema
with screening for prostate abnormalities if born male (as age Evidence Summary
appropriate). Clinicians should be familiar with the current CDC HIV testing
algorithms and interpretation of results based on algorithm and
Baseline Laboratory Evaluation assays used [75, 76]. Confirming an HIV diagnosis is especially
A number of initial laboratory studies are indicated upon pre- important in patients who are asymptomatic and have a normal
sentation with a new HIV diagnosis or for persons who reengage CD4 cell count and an undetectable or very low viral load. In
in care (see Table 4). Other tests may be indicated depending addition, patients may present to care with misinformation re-
on the age and sex of the patient and/or symptoms. In settings garding previous test results.
where rapid initiation of ART is possible, it is important to ob-
tain baseline laboratory tests. However, ART initiation need not CD4 Cell Counts and Percentages
Recommendations
be delayed until results are received, including for HIV RNA,
CD4 cell count, resistance testing, and safety assessments. The 7. A CD4 cell count with percentage should be obtained upon
absence of results for human leukocyte antigen subtype B*5701 initiation of care.
(HLA B*5701), genotype, and hepatitis B surface antigen will 8. Measurement of the CD8 cell count and the ratio of CD4 cells
influence the choice of antiretrovirals for rapid initiation. HIV to CD8 cells are unnecessary, as the results are not used in
diagnosis should be ascertained, preferably using rapid testing clinical decision-making.
with a fourth-generation antigen/antibody test if results of HIV
screening are not available for review.
Evidence Summary
HIV-Specific Tests for All Persons With HIV and HIV Screening The initial CD4 cell count is used to stage HIV infection,
Recommendation to help establish the risk of specific HIV-associated compli-
6. Patients who have no documentation of their HIV status cations, and to determine the need for prophylaxis against
or who were tested anonymously should have an HIV an- opportunistic infections. It is important that the clinician
tigen/antibody screening test performed upon initiation of and patient be aware of the substantial variation in CD4 cell
care. counts, especially during acute illness. CD4 cell counts may be
Test Comment(s)
Laboratory Tests to Assess Safety and General Health Screening for Coinfections and Screening for STIs
Recommendations Rates of STIs have increased substantially in the United States
17. A complete blood count with differential white blood cell since 2014, and screening rates have been found to be suboptimal
count, chemistry panel with calculated creatinine clearance (or in clinical care settings [85]. All clinicians who care for persons
estimated glomerular filtration rate [eGFR]) and glucose level, with HIV should implement CDC STI screening and treatment
and urinalysis should be obtained upon initiation of care. guidelines as appropriate for their populations [86]. CDC also
18. Because many antiretroviral drugs, HIV infection itself, and provides detailed recommendations for quality STI clinical serv-
host factors are associated with increased cholesterol and ices in primary care and STI specialty settings [87]. Persons diag-
triglyceride levels, a lipid profile should be obtained upon nosed with an STI should be encouraged to inform partners in
initiation of care and repeated fasting, if appropriate. order to decrease further transmission. Expedited partner therapy
(EPT), that is, the delivery of STI treatment directly to sexual part-
Evidence Summary
ners by the person diagnosed with an STI, should be considered.
Anemia, leukopenia, and thrombocytopenia are common
among persons with untreated HIV. The complete blood count Chlamydia, gonorrhea, trichomoniasis
also is used to calculate the absolute CD4 cell count. A chem- Recommendations
istry panel (including electrolytes, glucose, creatinine, blood 19. Persons with HIV should be screened for gonorrhea and
urea nitrogen, total protein, albumin, total bilirubin, aspartate chlamydia infection at initial presentation. Screening should
transaminase, and alanine transaminase) is an important tool include all sites of contact (oral, anal, urethral [urine], and
to assess renal and hepatic function and to look for evidence of vaginal). Those found to have gonorrhea or chlamydia
preexisting liver injury or hepatitis. on initial screening should be treated and rescreened in
Kidney function is abnormal in up to 30% of persons with 3 months because of high reinfection rates.
untreated HIV, and HIV-associated nephropathy is a relatively 20. All persons who have receptive vaginal sex should be
common cause of end-stage renal disease, especially in black screened for trichomoniasis at entry into care. Those found
persons with HIV, although both rates and mortality have to have trichomoniasis on initial screening should be
incarceration, and for those with chronic liver disease due to 33. Serologic screening for varicella zoster virus (VZV) may be con-
recent outbreaks in certain communities [99]. Prevaccination sidered for persons who have not had chicken pox or shingles
screening for HAV infection is cost-effective when there is a se- and who have not been previously vaccinated (see Section III).
roprevalence of >30% in the patient population [66]. Because
Evidence Summary
of worse outcomes for persons with HIV and HBV coinfection,
It is advisable to determine anti-varicella IgG levels for patients
persons with HIV who also have HBV should be adequately
who are unable to give a history of chicken pox or shingles [105,
treated for HBV [32]. Because many persons with HIV may
106].
be treated with tenofovir-based ART that also suppresses HBV,
stopping ART may result in a flair of HBV. Persons with HBV are Tests That May Be Performed Under Certain Circumstances: Chest
at higher risk for hepatocellular carcinoma (HCC) even in the Radiography
absence of cirrhosis. Screening for HCC in persons with HBV Recommendation
should be conducted according to the American Association 34. A baseline chest radiograph should be obtained in all per-
for the Study of Liver Diseases guidelines [97]. Persons not sons with HIV who have a positive tuberculosis screening
HIV-specific monitoring
HIV RNA Should be performed every 4–6 weeks after initiation of ART until
<50 copies/mL and then every 3–4 months. In patients with
consistent viral suppression and stable CD4 cell count for more
than 2 years, can be measured every 6 months [32].
CD4 cell count Every 3–6 months for the first 2 years after starting ART, or if
viremia develops, or if CD4 cell count <300/mm3. If CD4 cell
count 300–500/mm3 and HIV RNA suppressed for 2 years,
can be measured every 12 months. If CD4 cell count >500/
mm3 and HIV RNA suppressed for 2 years, measurement is
optional [32].
Screening for mental health and substance use issues
Depression screening Perform at least annually and when clinically appropriate Use standard depression screening tool such as Personal Health
varicella, administered 3 months apart) for adults and ado- Healthcare systems should maintain a record of current smoking
lescents with HIV with a CD4 cell count >200 cells/µL on status of patients. All clinicians should advise patients to stop
suppressive ART who do not have evidence of immunity to smoking and document this message at least yearly in the health
varicella [120, 150, 151]. Children should also receive the record. Referrals should be made for smoking cessation [155,
vaccine if aged >8 years and with a CD4 percentage ≥15% 156]. Although persons with HIV have increased rates of certain
[101]. Persons without evidence of immunity who have no cancers, recommendations for screening (prostate, breast, colon,
history of varicella or shingles and no history of vaccination lung) are not different than for the general population. Screening
against VZV and who are at risk of developing severe disease for hepatocellular carcinoma every 6 months by ultrasound with
or complications should receive VariZIG within 10 days or without alpha-fetoprotein is recommended for those with cir-
after exposure [101, 151, 152]. VariZIG can be obtained only rhosis from any cause [157]. Breast cancer is the second leading
under a treatment investigational new drug protocol (con- cause of cancer-related death in women in the United States after
tact FFF Enterprises at 1-800-843-7477). VariZIG is not in- lung cancer [158]. It does not appear to be increased in prevalence
dicated for persons who received 2 doses of varicella vaccine among women with HIV, although unusual clinical presentations
and became immunocompromised later in life [101, 120, and rapid progression have been reported, suggesting that breast
151]. Recombinant zoster vaccine should be administered to cancer may behave more aggressively in this setting (bilateral di-
adults aged >50 years using 2 doses 2 to 6 months apart for sease, poorly differentiated carcinoma, and early metastasis) [159].
the prevention of herpes zoster [153, 154]. Studies in HIV At present, screening mammography in persons with HIV should
have found the vaccine to be safe and immunogenic after 2 follow standard USPSTF guidelines [160].
doses. For persons aged between 21 and 29 years, cervical cancer
screening should be performed within 1 year of sexual debut
Screening for and Prevention of Cancer but not later than age 21 years or at the diagnosis of HIV. If the
Recommendations initial Pap smear is negative, some experts recommend a repeat
65. All patients who smoke should be strongly encouraged to Pap smear be performed within 6 to 12 months. If the results of
stop smoking and offered smoking cessation assistance. 3 consecutive Pap tests are normal, a follow-up Pap test should
Atorvastatin Caution (moderately increase atorvastatin’s Acceptable with appropriate dosing and monitoring; efavirenz [167] and
AUC) etravirine [168] decrease atorvastatin’s AUC; no data for nevirapine
Use lowest starting atorvastatin dose May need higher atorvastatin starting dose; doravirine does not affect levels of
atorvastatin [169]
Fluvastatin Not recommended with nelfinavir Acceptable with appropriate dosing and monitoring
Use of other protease inhibitors is allowed Etravirine may increase fluvastatin’s AUC [168]
with appropriate dosing and monitoring
May need lower fluvastatin starting dose with etravirine
No data on doravirine
Lovastatin Contraindicated (greatly increases lovastatin’s Acceptable with appropriate dosing and monitoring
AUC [170])
Decreases simvastatin’s AUC, so may need higher lovastatin starting dose
to be effective in improving BMD in small studies of persons In a meta-analysis that include 6 cross-sectional and 14 pre-post
with HIV, but the data are limited. It is important to exclude hormonal therapy studies, with a total of 487 transgender men
osteomalacia prior to initiating a bisphosphonate, as this could and 812 transgender women, hormone therapy had a neutral
lead to increased fragility and fracture. Common reasons for effect on BMD at all body sites evaluated, except for the lumbar
osteomalacia in this population are tenofovir-induced renal spine of transgender women, where a modest but significant in-
phosphate wasting and vitamin D deficiency, which have been crease was detected [186]. At this time, some programs recom-
reported in 40%–80% of persons with HIV. The spectrum and mend transgender people (regardless of birth-assigned sex) begin
severity of metabolic complications associated with vitamin D BMD screening at age 65. Screening between ages 50 and 64 years
deficiency among adult persons with HIV remain to be better should be considered for those with established risk factors for os-
characterized. Patients with vitamin D deficiency and osteo- teoporosis. Transgender people (regardless of birth-assigned sex)
penia by DXA should be treated with vitamin D and calcium who have undergone gonadectomy and have a history of at least
without bisphosphonates until the vitamin D deficiency has 5 years without hormone replacement should also be considered
resolved. A follow-up DXA should be repeated 1 year later to for BMD testing, regardless of age. Transgender people without
monitor the response to therapy. gonads who are not using hormone replacement should follow
There is insufficient evidence to guide recommendations for guidelines for agonadal or postmenopausal women, regardless of
BMD testing specific to transgender or gender-diverse individuals. birth-assigned sex or gender identity [187].
Recommendations
Prevention of Perinatal Transmission
Recommendations 85. Infants diagnosed with HIV should undergo HIV resist-
82. To prevent perinatal transmission, all pregnant persons ance testing prior to administering ART and, because of
with HIV should be treated with ART, regardless of their the rapid progression of disease, ART should be initiated
immunologic or virologic status. Therapy should be initi- as early as possible regardless of CD4 cell count, HIV RNA
ated as early as possible, preferably prior to conception. level, or clinical status.
83. Infants exposed to HIV in utero should be managed ac- 86. All children with HIV should initiate ART, regardless of
cording to DHHS perinatal guidelines. CD4 cell count/percentage, HIV RNA level, or symptoms.
87. CD4 cell counts and HIV RNA should be monitored no less
Evidence Summary than every 3–4 months in infants and children.
Perinatal transmission of HIV is preventable if pregnant per- 88. Childhood vaccinations should be administered according
sons are screened and identified through antenatal HIV testing to ACIP schedules for infants and children with HIV.
and receive immediate ART according to DHHS perinatal 89. Infants and children with HIV should be managed by a spe-
guidelines [117]. In those who start ART before conception and cialist with knowledge of the unique therapeutic, pharma-
maintain viral load suppression, there is essentially zero risk of cologic, behavioral, psychosocial, and developmental issues
perinatal transmission [204]. associated with HIV.
Gender/sex: broad terms describing the entire category of relevant biological characteristics, self-identification, and stereotypical behaviors that might
be considered male, female, or some variation
Gender identity: the internal sense of being male, female, or neither
Transgender, transsexual, trans, gender nonbinary, gender diverse, gender incongruent, genderqueer: adjectives used to refer to persons whose
gender identity does not align with their sex recorded at birth (the latter primarily based on visible physical anatomy)
Cisgender, nontransgender: adjectives used to refer to persons whose gender identity aligns with their sex recorded at birth
Gender expression: how a person communicates gender identity through appearance, dress, name, pronouns, mannerisms, and speech
Gender-affirming hormone treatment and surgeries: broad categories of medical interventions that transgender persons might consider to align their
appearance and their gender identity
Gender transition, gender affirmation, gender confirmation: an overall process of alignment of physical characteristics and/or gender expression with
gender identity
Gender dysphoria: discomfort felt by some persons due to lack of alignment between gender identity and the sex recorded at birth; not all transgender
persons have dysphoria, but many US insurance companies require this diagnosis for payment for transgender medical and surgical interventions
Feminizing hormone therapy: the use of estrogens and often androgen blockers with the objective of inducing changes in physical characteristics to
better match patient gender identity
Masculinizing hormone therapy: the use of testosterone with the objective of inducing changes in physical characteristics to better match patient
gender identity
Adapted from [224].
Table 8. Standards of Care for the Health of Transsexual, Transgender, and Gender-diverse Persons
• Exhibit respect for patients who are transgender and gender-diverse (do not pathologize differences in gender identity or expression)
• Provide care (or refer to knowledgeable colleagues) that affirms patients’ gender identities and reduces the distress of gender dysphoria, when present
• Become knowledgeable about the healthcare needs of transsexual, transgender, and gender-nonconforming people, including the benefits and risks of
treatment options for gender dysphoria
• Match the treatment approach to the specific needs of patients, particularly their goals for gender expression and need for relief from gender dysphoria
• Facilitate access to appropriate care
• Seek patients’ informed consent before providing treatment
• Offer continuity of care
• Be prepared to support and advocate for patients within their families and communities (schools, workplaces, and other settings)
Adapted from [70].