Chronic retroviral infection of CD4 T-cells leading to progressive immunodeficiency; managed with lifelong combination antiretroviral therapy.
Also known as: HIV, AIDS, human immunodeficiency virus, acquired immunodeficiency syndrome
Overview
Infection with HIV-1 or HIV-2, single-stranded RNA retroviruses that bind CD4 and CCR5/CXCR4 to infect helper T-cells, monocytes, and dendritic cells. AIDS is defined as HIV infection plus CD4 count <200 cells/uL or the presence of an AIDS-defining illness.
Epidemiology
Approximately 1.2 million people in the US live with HIV; roughly 13% are undiagnosed. New infections concentrated among men who have sex with men, injection drug users, and Black and Latino populations in the South. HIV-1 dominates worldwide; HIV-2 largely restricted to West Africa.
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Multiple sex partners, condomless sex, concurrent STI (especially ulcerative — syphilis, HSV)
Injection drug use with shared needles
Vertical transmission (in utero, intrapartum, breastfeeding) — risk reduced from ~25% to <1% with maternal ART
Occupational needlestick (per-exposure risk ~0.3% for hollow-bore blood exposure)
Blood transfusion in regions without universal screening
Pathophysiology
Envelope gp120 binds CD4 and a coreceptor (CCR5 in early infection, CXCR4 later), allowing gp41-mediated fusion and viral entry. Reverse transcriptase produces proviral DNA that integrates into the host genome via integrase. Ongoing replication depletes CD4 cells, disrupts lymph node architecture, and causes chronic immune activation. Untreated, CD4 declines ~50-100 cells/uL/year; opportunistic infections appear as immunity fails.
Acute mononucleosis-like illness 2-4 weeks after high-risk exposure, often with a non-pruritic trunk rash, should prompt HIV RNA testing even if antibody screening is negative.
Differential diagnosis
Acute viral syndrome (EBV, CMV, acute hepatitis) — Acute retroviral syndrome mimics mononucleosis; obtain HIV RNA viral load (turns positive ~10 days) — antibody tests miss the window period
Secondary syphilis — Diffuse maculopapular rash including palms/soles, mucous patches, condyloma lata; RPR/VDRL plus treponemal test
Lymphoma — Persistent lymphadenopathy, B symptoms; biopsy required — HIV-associated lymphomas common at low CD4
Idiopathic CD4 lymphocytopenia — Low CD4 with negative HIV tests; rare diagnosis of exclusion
Tuberculosis — Coinfection extremely common worldwide; screen all newly diagnosed HIV with IGRA or TST and CXR
Diagnostic workup
Diagnostic criteria
CDC algorithm: reactive Ag/Ab combo assay confirmed by HIV-1/2 differentiation assay. Discordant or early-infection cases resolved with HIV RNA. AIDS = HIV plus CD4 <200 cells/uL or any stage-3 AIDS-defining condition.
AIDS-defining malignancies — Kaposi sarcoma, non-Hodgkin lymphoma, invasive cervical cancer
HIV-associated neurocognitive disorder (HAND)
Immune reconstitution inflammatory syndrome (IRIS) within weeks of starting ART
Accelerated atherosclerosis, CKD (especially with TDF), osteoporosis, metabolic syndrome
PANCE pearls
Acute HIV: antibody-based tests can be negative in the window period — order HIV RNA viral load.
Pregnancy: dolutegravir is now preferred throughout pregnancy (early neural tube signal not confirmed). Avoid TAF in late pregnancy data-poor scenarios; TDF/FTC + dolutegravir is well-validated.
U = U: undetectable equals untransmittable. Sustained viral suppression eliminates sexual transmission risk (PARTNER, PARTNER2, Opposites Attract trials).
Cryptococcal meningitis: opening pressure is therapeutic — serial LPs reduce mortality more than any antifungal change.
References
DHHS 2024 — Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV (clinicalinfo.hiv.gov)
CDC 2014 — Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations (MMWR)
START Trial — Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (NEJM 2015)
PARTNER2 — Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (Rodger et al., Lancet 2019)
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