Infectious Disease
HIV Infection
Pathogenesis of an immune-destroying retrovirus and the antiretroviral revolution
HIV is a retrovirus that targets CD4+ T helper cells via the CD4 receptor and CCR5 or CXCR4 coreceptors. Reverse transcriptase converts viral RNA to DNA; integrase inserts proviral DNA into the host genome. Without treatment, CD4 count falls progressively over a decade; AIDS is defined by CD4 <200 cells/µL or AIDS-defining illness. Acute infection causes mononucleosis-like syndrome 2-4 weeks after exposure with high viremia. After seroconversion, clinical latency lasts years before opportunistic infections — Pneumocystis jirovecii, cryptococcal meningitis, CMV retinitis, Kaposi sarcoma, MAC. Antiretroviral therapy (ART) suppresses replication, allowing CD4 recovery and near-normal life expectancy. Modern regimens are typically single-tablet — bictegravir/emtricitabine/tenofovir alafenamide. U=U: undetectable viral load means untransmittable.
- TargetCD4+ T cells via CD4/CCR5/CXCR4
- GenomeSingle-stranded RNA retrovirus
- AIDS thresholdCD4 <200 cells/µL
- Window period10 days HIV RNA; 2-4 weeks antibody
- First ARTZidovudine (AZT) 1987
- Modern regimenSingle-tablet integrase inhibitor + 2 NRTIs
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Why HIV care matters
- Universal screening. Routine testing identifies undiagnosed HIV.
- Acute infection. Mono-like illness in at-risk patient — test HIV RNA.
- Treatment as prevention. Suppression eliminates transmission.
- PrEP and PEP. Reduces incidence in high-risk populations.
- Opportunistic infections. Recognize at threshold CD4 counts.
- Drug interactions. Boosted PIs interact with statins, anticonvulsants, contraceptives.
- Comorbidities. CV, renal, hepatic, neurocognitive monitoring.
Common errors
- Missing acute HIV. Mono-like illness needs HIV RNA, not just antibody.
- Stopping PrEP for STI risk only. PrEP doesn't prevent other STIs but still prevents HIV.
- Calling viral load failure resistance without adherence assessment. Most failures are nonadherence.
- Discontinuing ART for IRIS. Treat the IRIS; don't stop ART.
- Inadequate PEP timing. Within 72 hours; sooner the better.
- Stigmatizing language. Say "person with HIV," not "HIV patient."
Frequently asked questions
How does HIV destroy the immune system?
HIV infects CD4+ T cells, macrophages, dendritic cells. Direct cytolysis from viral budding; immune-mediated killing of infected cells; pyroptosis from abortive infection of resting T cells (drives chronic inflammation). CD4 count falls. Below 500 — increased zoster, TB, bacterial infections. Below 200 — Pneumocystis, candida. Below 100 — toxoplasmosis, cryptococcus, MAC. Below 50 — CMV retinitis. Chronic immune activation persists even on ART; contributes to cardiovascular and neurologic disease.
How does ART work?
Combination of drugs targeting different viral steps prevents resistance. NRTIs (tenofovir, emtricitabine, abacavir, lamivudine) — chain terminators of reverse transcriptase. NNRTIs (efavirenz, rilpivirine, doravirine) — bind RT allosterically. Integrase inhibitors (bictegravir, dolutegravir, raltegravir) — first-line. Protease inhibitors (darunavir/r) — block viral maturation. Entry inhibitors — maraviroc (CCR5), enfuvirtide (fusion). Pharmacokinetic boosters — ritonavir, cobicistat. Modern regimens — INSTI + 2 NRTIs in single tablet.
How is HIV transmitted?
Sexual contact (vaginal, anal, oral — receptive anal highest risk), shared needles, perinatal (in utero, delivery, breastfeeding), blood transfusion (now extremely rare with screening), occupational needlestick (~0.3% per exposure). Cofactors increase risk — STIs, ulcerative lesions, high viral load. Acute infection has highest transmissibility (very high viral load before antibodies). Treatment as prevention — undetectable viral load on ART eliminates sexual transmission (U=U).
What is PrEP?
Pre-exposure prophylaxis. Daily emtricitabine/tenofovir disoproxil (Truvada) or emtricitabine/tenofovir alafenamide (Descovy) reduces HIV acquisition by ~99% with adherence. Long-acting injectable cabotegravir every 2 months — superior in adherent populations. PEP — post-exposure prophylaxis after high-risk exposure; start within 72 hours, continue 28 days; tenofovir/emtricitabine plus dolutegravir or raltegravir. PrEP requires HIV testing every 3 months, renal function, STI screening.
What about HIV testing?
Fourth-generation antigen-antibody assay detects p24 antigen and antibodies — positive 2-3 weeks post-exposure. HIV RNA detectable within 10 days. Confirmatory HIV-1/2 differentiation immunoassay. Window period — false negative possible early. Acute HIV requires HIV RNA. Patients with mono-like illness, recent risk exposure should be tested with both antibody and RNA. Universal opt-out screening recommended for all adults at least once.
What are opportunistic infections?
Infections that exploit immunosuppression. PCP (Pneumocystis jirovecii) at CD4 <200 — bilateral interstitial infiltrates, hypoxia; treat TMP-SMX 15-20 mg/kg/day; steroids if PaO2 <70. Toxoplasmosis at CD4 <100 — ring-enhancing brain lesions; pyrimethamine + sulfadiazine + leucovorin. Cryptococcal meningitis — induction amphotericin B + flucytosine. MAC at CD4 <50 — clarithromycin + ethambutol ± rifabutin. CMV retinitis — ganciclovir or valganciclovir. Prophylaxis with TMP-SMX, azithromycin until CD4 recovery.
What is U=U?
Undetectable equals untransmittable. Sustained viral suppression on ART (HIV RNA <200 copies/mL for 6+ months) eliminates sexual transmission of HIV — proven by HPTN 052, PARTNER, PARTNER 2, Opposites Attract studies. Major public health and stigma-reduction message. Does not yet apply with same certainty to perinatal transmission (further reduction with C-section, formula feeding in resource settings) or sharing needles. Forms basis of treatment-as-prevention strategy.