HIV infection is caused by HIV-1 (most common) or HIV-2, retroviruses that target CD4+ T-lymphocytes leading to progressive immune dysfunction and AIDS without treatment. Global epidemic affects ~39 million people. Transmission via sexual contact, parenteral (IDU, blood products), and vertical (mother-to-child). Natural history without treatment: acute retroviral syndrome (2-4 weeks post-exposure, mononucleosis-like), clinical latency (median 8-10 years), AIDS (CD4<200, opportunistic infections, malignancies). Modern ART has transformed HIV from fatal to chronic manageable disease with near-normal life expectancy when treated early.
Initial evaluation includes confirmed HIV diagnosis (4th-generation Ag/Ab assay, confirmatory differentiation, RNA if early), baseline labs (CD4, HIV RNA, genotype resistance testing, HLA-B*5701 if abacavir considered, basic chemistries, hepatitis B/C screening, syphilis, gonorrhea, chlamydia, TB screening), comorbidity assessment (CVD risk, renal function, liver function, bone density), and immunizations (pneumococcal, influenza, HBV, HAV, HPV, MMR/VZV if non-immune and CD4 adequate). Mental health, substance use, and social support evaluation are essential.
Antiretroviral therapy is recommended for all HIV-infected individuals regardless of CD4 count (Universal ART). Preferred first-line regimens (DHHS/IAS-USA 2024): bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC, Biktarvy) single-tablet, dolutegravir + emtricitabine + tenofovir alafenamide or disoproxil (DTG + TAF/FTC or TDF/FTC), dolutegravir/lamivudine (DTG/3TC, Dovato) for treatment-naive without HBV coinfection or HIV RNA <500,000 with no archived resistance. INSTI-based regimens are preferred for high efficacy, low resistance barrier, tolerability, and minimal drug interactions. Cabotegravir/rilpivirine long-acting injectable (Cabenuva, every 1-2 months) is option for virally suppressed patients. Monitoring: HIV RNA every 3-6 months (goal undetectable, <50 copies/mL), CD4 every 6-12 months (less frequently if stable >300), comprehensive metabolic, lipids, urinalysis, bone density, STI screening per risk. Opportunistic infection prophylaxis: TMP-SMX for PCP/toxoplasmosis if CD4<200, azithromycin for MAC if CD4<50 (less commonly used in ART era), TB preventive therapy. U=U (Undetectable=Untransmittable): patients with sustained undetectable viral load do not sexually transmit HIV. Pre-exposure prophylaxis (PrEP): emtricitabine/TDF or TAF, cabotegravir LA injectable for at-risk HIV-negative individuals. Post-exposure prophylaxis (PEP): tenofovir/emtricitabine + raltegravir or dolutegravir for 28 days, started within 72 hours.