Residency · Residency · Internal Medicine
HIV Fundamentals for the Internist
Introduction
Human immunodeficiency virus (HIV) infection remains a critical diagnosis for internists to recognize, manage, and screen for. With modern antiretroviral therapy (ART), HIV has become a chronic manageable disease, yet late diagnosis continues to drive morbidity and mortality. Every internist must be proficient in screening, initial evaluation, opportunistic infection prophylaxis, and ART fundamentals.
Epidemiology and Screening
Current Landscape
- Approximately 1.2 million people in the United States are living with HIV; an estimated 13% are unaware of their status
- Men who have sex with men (MSM) account for the majority of new diagnoses
- Racial and ethnic disparities persist, with disproportionate burden on Black and Hispanic populations
Screening Recommendations
- CDC and USPSTF recommend universal screening for all adults aged 15-65 at least once
- High-risk individuals should be screened at least annually
- Fourth-generation antigen/antibody combination assay is the recommended initial test
- Reactive screening test followed by HIV-1/HIV-2 differentiation immunoassay
- If discordant results, obtain HIV-1 RNA (viral load) to resolve
Initial Evaluation of a New HIV Diagnosis
Baseline Laboratory Studies
- CD4 count and percentage: guides opportunistic infection risk and prophylaxis
- HIV viral load (RNA): baseline for monitoring ART response
- Genotypic resistance testing: essential before initiating ART
- CBC, CMP, lipid panel, urinalysis, HbA1c
- Hepatitis A, B, and C serologies; syphilis screening (RPR); tuberculosis screening (IGRA preferred)
- Toxoplasma IgG, CMV IgG; cervical or anal cancer screening as appropriate
Immunization Assessment
- Update all age-appropriate vaccines; avoid live vaccines if CD4 < 200
- Pneumococcal vaccination (PCV20 or PCV15 + PPSV23)
- Annual influenza; hepatitis A and B if non-immune; HPV through age 45
Antiretroviral Therapy
Principles of ART
- ART should be initiated in all patients with HIV regardless of CD4 count
- Rapid ART initiation (same day or within 7 days) improves linkage to care and outcomes
- Goal: achieve undetectable viral load (< 200 copies/mL) within 8-24 weeks
- U = U (Undetectable = Untransmittable): persons with sustained viral suppression do not transmit HIV sexually
Preferred Initial Regimens
- Bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy): preferred single-tablet regimen
- Dolutegravir + emtricitabine/tenofovir (either TAF or TDF formulation)
- Integrase strand transfer inhibitors (INSTIs) are the preferred anchor class
- Consider renal function, bone density, and hepatitis B status when selecting NRTI backbone
Opportunistic Infection Prophylaxis
CD4-Based Prophylaxis Thresholds
| CD4 Threshold | Infection | Prophylaxis | Discontinuation |
|---|---|---|---|
| < 200 | PJP (Pneumocystis) | TMP-SMX DS daily | CD4 > 200 for ≥ 3 months |
| < 100 + Toxo IgG+ | Toxoplasmosis | TMP-SMX DS daily (dual coverage) | CD4 > 200 for ≥ 3 months |
| < 50 | MAC | Azithromycin 1200 mg weekly | CD4 > 100 for ≥ 3 months |
- CD4 < 200: Pneumocystis jirovecii pneumonia (PJP) prophylaxis with TMP-SMX DS daily
- CD4 < 100 + positive Toxoplasma IgG: TMP-SMX DS daily provides dual coverage
- CD4 < 50: Mycobacterium avium complex (MAC) prophylaxis with azithromycin 1200 mg weekly (if ART not immediately initiated)
- Discontinue prophylaxis when CD4 sustained > 200 for at least 3 months on ART
Key Opportunistic Infections to Recognize
- PJP: progressive dyspnea, dry cough, bilateral ground-glass opacities, elevated LDH
- Cryptococcal meningitis: subacute headache, elevated opening pressure on LP
- CMV retinitis: floaters, visual field deficits; CD4 typically < 50
- Cerebral toxoplasmosis: ring-enhancing lesions on MRI, positive Toxoplasma IgG
Immune Reconstitution Inflammatory Syndrome (IRIS)
- Paradoxical clinical worsening after ART initiation due to immune recovery
- Most common in patients with low baseline CD4 counts and high viral loads
- TB-IRIS and Cryptococcal-IRIS are the most clinically significant forms
- Management: continue ART, treat underlying infection, corticosteroids in severe cases
Pre-Exposure Prophylaxis (PrEP)
- Emtricitabine/tenofovir disoproxil fumarate (Truvada) or emtricitabine/tenofovir alafenamide (Descovy) for daily oral PrEP
- Cabotegravir long-acting injectable: every 2 months; superior efficacy in trials
- Screen for HIV, renal function, and hepatitis B before initiation
- Internists should identify eligible patients and offer or refer for PrEP
Key Clinical Pearls
- Universal HIV screening is standard of care; do not limit testing to perceived risk groups
- Initiate ART as soon as possible; same-day starts improve retention in care
- Always check genotypic resistance before selecting an ART regimen
- TMP-SMX for PJP prophylaxis also covers Toxoplasma; know when to start and stop
- Undetectable viral load means untransmittable; communicate this to patients
References
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Updated 2025.
- Saag MS, Gandhi RT, Hoy JF, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2020 recommendations of the International Antiviral Society-USA panel. JAMA. 2020;324(16):1651-1669.
- US Preventive Services Task Force. Screening for HIV infection: US Preventive Services Task Force recommendation statement. JAMA. 2019;321(23):2326-2336.
- Landovitz RJ, Donnell D, Clement ME, et al. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med. 2021;385(7):595-608.