Residency · Residency · Internal Medicine

HIV Fundamentals for the Internist

Start here

Alright, future attending, pull up a chair. You just got paged about a new admission, a 34-year-old male, here for a vague cough and some fevers, and oh, by the way, his rapid HIV test just came back reactive. You’re tired, it’s 2 AM, and your brain is already picturing the next patient. Breathe. This isn't the emergency you might imagine. Your immediate job is to stabilize, not to become an overnight expert in Human Immunodeficiency Virus. First, is he crashing? Any severe respiratory distress suggesting Pneumocystis Jirovecii Pneumonia (PJP)? Any focal neurological deficits or altered mental status hinting at something like cerebral toxoplasmosis or cryptococcal meningitis? If not, he’s probably stable enough to wait for the light of day.

Your next thought should be about baseline labs. While you wait for definitive testing, ensure a CD4 count and HIV viral load are on their way. These will tell you how advanced his disease is and give you a baseline for monitoring treatment. Don't forget genotypic resistance testing; we need to know what drugs will actually work. If his CD4 count is critically low, say, below 200 cells/µL, you'll need to consider starting opportunistic infection prophylaxis. The workhorse here is trimethoprim-sulfamethoxazole (TMP-SMX) for PJP, and it also covers Toxoplasma gondii if he’s seropositive for it and his CD4 is below 100.

Finally, remember the big picture. With modern antiretroviral therapy (ART), HIV is a chronic, manageable condition. Your role right now is to ensure he's safe, get the diagnostic ball rolling, and set him up for a smooth transition to treatment. Most importantly, reassure him. Let him know that many people live long, healthy lives with HIV, and that you and the team are there to guide him through this. The rest, the nuances of choosing specific ART regimens, vaccination schedules, and discussing "undetectable = untransmittable" (U=U), can wait until a clearer, less exhausted tomorrow.

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 < 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

1. 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.
2. 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.
3. US Preventive Services Task Force. Screening for HIV infection: US Preventive Services Task Force recommendation statement. JAMA. 2019;321(23):2326-2336.
4. 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.

For the intern

When consulted overnight about a newly diagnosed HIV patient, your priorities are straightforward. Ensure the patient is clinically stable and assess for acute opportunistic infections—fever, respiratory distress, altered mental status, or visual changes require immediate workup. Check the CD4 count if available; if CD4 is below 200, start PJP prophylaxis with TMP-SMX. Confirm baseline labs are ordered (CD4, viral load, resistance testing, hepatitis and syphilis serologies). Most other tasks—initiating ART, completing vaccination updates, arranging infectious disease follow-up—can wait until morning rounds. Document the new diagnosis clearly and ensure appropriate precautions are in place, though remember that standard precautions are sufficient for routine care.

Common pitfalls

• Delaying ART initiation unnecessarily: Modern guidelines recommend rapid start (within days), not waiting weeks for subspecialty appointments. Identify and address barriers to same-week initiation.

• Forgetting hepatitis B status before selecting regimen: Some ART agents treat hepatitis B; discontinuing them in coinfected patients risks hepatitis flare. Always check HBsAg before choosing tenofovir-containing regimens.

• Starting prophylaxis without checking CD4: Not every HIV patient needs PJP prophylaxis immediately. Wait for CD4 results rather than reflexively prescribing TMP-SMX to all newly diagnosed patients.

• Misunderstanding transmission risk: Patients with undetectable viral load on ART cannot transmit HIV sexually (U=U). Communicate this clearly—it profoundly impacts patient counseling and reduces stigma.

Make it stick

You’re on call, and a new human immunodeficiency virus (HIV) diagnosis just hit your pager. What do you do? First, breathe. Your immediate job is to stabilize, not cure. Is the patient acutely ill with an opportunistic infection? Look for fever, cough, mental status changes, or vision loss. Second, ensure baseline labs are drawn: CD4 count, HIV viral load, and genotypic resistance testing are crucial. If the CD4 is <200, start Pneumocystis jirovecii pneumonia (PJP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). Everything else—vaccines, specific antiretroviral therapy (ART) regimen selection, and long-term planning—can wait for morning rounds or infectious disease consultation. Your role is to prevent immediate harm and set the stage for comprehensive care.

If you remember one thing

Prioritize acute stabilization and PJP prophylaxis if the CD4 count is low; all other aspects of HIV management, including selecting specific ART, can typically be deferred to the day team or subspecialists. Never delay rapid ART initiation due to waiting for follow-up appointments unless there is an overwhelming medical contraindication.

Read this lecture as Markdown