Clinical meaning
The CDC-recommended HIV testing algorithm uses a sequential three-step approach. Step 1: 4th generation HIV-1/2 Ag/Ab combination immunoassay — detects both HIV-1/2 antibodies AND p24 antigen, shortening the window period to approximately 18 days. If reactive, proceed to Step 2: HIV-1/2 antibody differentiation immunoassay — confirms and differentiates HIV-1 from HIV-2. If Step 2 is nonreactive or indeterminate, proceed to Step 3: HIV-1 RNA qualitative or quantitative nucleic acid test (NAT) — detects viral RNA directly, confirming or ruling out acute HIV-1 infection during the window period. This algorithm replaces the older Western blot confirmatory test. Rapid point-of-care tests detect antibodies only and have a longer window period; reactive rapid tests require laboratory confirmation. The acute retroviral syndrome presents 2-4 weeks post-infection with a mononucleosis-like illness (fever, pharyngitis, lymphadenopathy, maculopapular rash, myalgia, oral ulcers). During ARS, viral load is extremely high (>10⁶ copies/mL) making the patient highly infectious, but antibody tests may still be negative. Screening recommendations: opt-out HIV testing for ALL persons aged 13-64 at least once; annual for high-risk populations.