Which test detects acute HIV infection when the initial 4th-gen test is reactive but the differentiation assay is negative?

• A. Western blot
• B. ELISA
• C. Nucleic acid test (NAT)
• D. CD4 count

Answer: (C)

During acute HIV infection, the virus is already circulating, but the body's antibody response may not be detectable yet. A fourth-generation test can be reactive by detecting either HIV antibodies or the p24 antigen, but if the differentiation assay for antibodies is negative, it suggests that antibodies haven’t developed despite viral presence. The test that directly detects the virus itself—HIV RNA in the blood—is the best way to confirm acute infection in this window. Western blot and ELISA rely on antibodies and can be negative early on, so they aren’t reliable for confirming acute infection. CD4 count reflects immune status, not infection detection. So, a nucleic acid test measuring HIV RNA is the appropriate next step to confirm acute HIV infection.