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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Screen with fourth-generation HIV-1/2 antigen-antibody immunoassay; confirm with HIV-1/2 differentiation assay and HIV RNA if discordant
- AIDS is defined by CD4 <200 cells/mm3, CD4 percentage <14%, or an AIDS-defining illness
- Start ART immediately in essentially all patients, including most opportunistic infections; do not wait for CD4 recovery
- Preferred initial ART usually includes an INSTI-based regimen such as bictegravir-tenofovir alafenamide-emtricitabine or dolutegravir plus two NRTIs
- Before ART: HIV RNA, CD4 count, resistance genotype, HLA-B*5701 if abacavir considered, hepatitis serologies, renal/liver tests, STI screening, TB screening, pregnancy test when relevant
- Step 2 CK pearl: acute retroviral syndrome can mimic mononucleosis but often has mucocutaneous ulcers, rash, and very high HIV RNA with initially negative antibody testing
Overview
HIV is a lentiviral infection transmitted through sexual exposure, blood exposure, and perinatal routes. It infects CD4 T lymphocytes and macrophages, causing progressive immune dysfunction without treatment. Modern antiretroviral therapy suppresses HIV replication, restores immune function, prevents opportunistic infections, and prevents sexual transmission when viral suppression is sustained. US practice emphasizes opt-out screening, rapid linkage to care, same-day or rapid ART when feasible, and longitudinal monitoring of HIV RNA and CD4 count.
Epidemiology
More than 1 million people live with HIV in the United States. Transmission is concentrated among men who have sex with men, persons with injection drug use, heterosexual contacts with high-risk exposure, and perinatal exposure. Late diagnosis remains important for examinations because patients may first present with thrush, Pneumocystis pneumonia, cryptococcal meningitis, wasting, Kaposi sarcoma, or unexplained lymphadenopathy.
Clinical Features
Symptoms
Acute HIV: fever, sore throat, lymphadenopathy, myalgias, headache, diarrhea, rash, and painful mucocutaneous ulcers 2-4 weeks after exposure
Chronic HIV: may be asymptomatic for years with persistent generalized lymphadenopathy
Advanced disease: weight loss, chronic diarrhea, fever, night sweats, oral candidiasis, recurrent infections
Neurologic symptoms: cognitive slowing, peripheral neuropathy, aseptic meningitis, or opportunistic CNS disease
Respiratory symptoms in advanced HIV: dyspnea and dry cough suggest PCP; focal pneumonia may be bacterial or TB
Visual floaters or vision loss in CD4 <50 suggests CMV retinitis
Signs
Generalized non-tender lymphadenopathy involving >=2 noncontiguous sites
Oral thrush or oral hairy leukoplakia
Seborrheic dermatitis, molluscum contagiosum, herpes zoster, or Kaposi sarcoma lesions
Cachexia, fever, or hepatosplenomegaly in advanced disease
Focal neurologic deficits, meningismus, or altered mental status in advanced immunosuppression
Investigations
First-line
Fourth-generation HIV-1/2 Ag/Ab immunoassayPreferred screening test; detects p24 antigen and antibodies, shortening the window period compared with antibody-only tests
HIV-1/HIV-2 antibody differentiation immunoassayConfirmatory test after a reactive screening assay; distinguishes HIV-1 from HIV-2
HIV RNA viral loadUsed when acute infection is suspected or screening/confirmatory tests are discordant; also baseline and treatment monitoring
CD4 count and percentageStages immune suppression and guides OI prophylaxis; repeat every 3-6 months until stable viral suppression and immune recovery
Second-line
Baseline genotype resistance testingRecommended before ART; do not delay rapid ART in most cases while awaiting results unless concern for complex resistance
Baseline safety and coinfection labsCBC, CMP, creatinine/eGFR, urinalysis if tenofovir, fasting lipids/glucose, hepatitis A/B/C serologies, TB screening, STI testing, pregnancy test
HLA-B*5701Required before abacavir because positive patients are at high risk of abacavir hypersensitivity
Specialist
HIV specialist referralNeeded for pregnancy, opportunistic infection, renal/hepatic disease, suspected resistance, HIV-2, or complex drug interactions
Lumbar puncture / imagingIf neurologic symptoms suggest cryptococcal meningitis, toxoplasmosis, CNS lymphoma, neurosyphilis, or TB meningitis
1
Immediate linkage and prevention
- Offer opt-out testing in health care settings; use risk-based repeat testing for ongoing exposure
- Counsel that sustained undetectable viral load prevents sexual transmission (U=U)
- Notify and test partners; screen for STIs, hepatitis B/C, TB, and pregnancy
- Offer PrEP to HIV-negative partners at risk and PEP within 72 hours after significant exposure
2
Initial ART
- Start ART as soon as possible after diagnosis, often same day if no contraindication
- Preferred regimens commonly include bictegravir/TAF/emtricitabine or dolutegravir plus TAF/emtricitabine or TDF/emtricitabine
- Dolutegravir/lamivudine is an option only if HIV RNA <=500,000, no hepatitis B coinfection, and genotype/HBV results available
- Avoid abacavir unless HLA-B*5701 negative and cardiovascular risk has been considered
- If hepatitis B coinfection: regimen must include tenofovir plus emtricitabine or lamivudine to prevent HBV flare
3
Monitoring
- Check HIV RNA 2-4 weeks after starting or changing ART, then every 4-8 weeks until suppressed
- After suppression, monitor HIV RNA every 3-6 months
- CD4 every 3-6 months initially; may space out or stop frequent testing after sustained suppression and CD4 >300-500
- Virologic failure = inability to suppress or rebound; assess adherence, interactions, resistance, and access barriers
4
OI prophylaxis by CD4 count
- CD4 <200 or oropharyngeal candidiasis: TMP-SMX for PCP prophylaxis
- CD4 <100 and Toxoplasma IgG positive: TMP-SMX also prevents toxoplasmosis
- CD4 <50: MAC prophylaxis with azithromycin only if not immediately starting effective ART or if viremia persists without options
- Vaccinate early: influenza, COVID, pneumococcal, hepatitis A/B, HPV, meningococcal as indicated; avoid live vaccines with CD4 <200
Complications
- Opportunistic infections: PCP, toxoplasmosis, cryptococcosis, CMV, MAC, TB, histoplasmosis
- Malignancy: Kaposi sarcoma, non-Hodgkin lymphoma, cervical/anal cancer
- Neurologic disease: HIV-associated neurocognitive disorder, distal symmetric polyneuropathy, PML
- Metabolic and cardiovascular disease: Dyslipidemia, insulin resistance, renal disease, and increased ASCVD risk
- Immune reconstitution inflammatory syndrome: Paradoxical worsening of occult or treated infection after ART initiation, especially TB, MAC, and cryptococcus
USMLE Step 2 CK Exam Tips
- 1Acute HIV = mono-like illness + rash + mucocutaneous ulcers after exposure. Best test is HIV RNA if Ag/Ab is negative or indeterminate
- 2AIDS is CD4 <200 or AIDS-defining illness, not just a positive HIV test
- 3Start ART immediately for most patients; major Step 2 exceptions involve careful timing in cryptococcal or TB meningitis
- 4HLA-B*5701 must be checked before abacavir; positive = never use abacavir
- 5Tenofovir/emtricitabine treats hepatitis B; stopping it in HBV coinfection can cause severe hepatitis flare
- 6TMP-SMX prophylaxis starts at CD4 <200 and also covers toxoplasmosis when CD4 <100 and Toxo IgG positive
- 7Undetectable viral load = effectively no sexual transmission risk; still continue STI screening and prevention counseling
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