Acute HIV-1 Infection: Answer D
The correct answer is D) HIV-1 Ab negative, HIV-1 NAT positive, which represents the classic laboratory pattern of acute HIV-1 infection during the "window period" when viral RNA is detectable but antibodies have not yet developed. 1
Understanding the Diagnostic Timeline
The sequence of marker appearance in acute HIV-1 infection follows a predictable pattern:
- HIV-1 RNA (NAT) becomes detectable first, typically 10-14 days after infection 1
- p24 antigen appears 3-5 days after HIV RNA, usually between 14-22 days post-infection 1
- HIV antibodies develop last, typically within the first 4 weeks following exposure but can take up to 6 months 1
Why Each Answer is Correct or Incorrect
Option A (HIV-1/2 Ab negative, p24 Ag negative): This represents either no infection or the very earliest stage of infection (within 10-14 days) when no markers are yet detectable—the true "eclipse period" 1. This does not indicate acute HIV-1 infection diagnostically.
Option B (HIV-1 Ab positive, HIV-2 Ab negative): This indicates established HIV-1 infection with seroconversion already complete, not acute infection 1. By the time antibodies are positive, the patient has moved beyond the acute phase.
Option C (HIV-1 Ab indeterminate, HIV-1 NAT negative): An indeterminate antibody result with negative NAT is more likely a false-positive antibody result or cross-reactivity rather than acute infection 1. True acute infection would show positive NAT.
Option D (HIV-1 Ab negative, HIV-1 NAT positive): This is the definitive pattern of acute HIV-1 infection 1. The laboratory diagnosis of primary (acute) HIV-1 infection is based on detection of HIV-1 RNA (typically >100,000 copies/mL) in the absence of antibodies 1.
Clinical Significance and Testing Algorithm
- When acute HIV infection is suspected clinically, HIV RNA testing should be performed after a negative initial antibody and/or antigen test 1
- The current CDC-recommended algorithm uses fourth-generation Ag/Ab combination assays as initial screening, followed by HIV-1/HIV-2 antibody differentiation 1
- If the differentiation assay is negative (antibodies not detected), NAAT is recommended to rule out acute HIV-1 infection 1
- HIV-1 qualitative NAAT is recommended in specific cases based on the antibody/antigen and differentiation test results 1
Important Caveats
- There is a 10-14 day period after infection when no markers are detectable; testing another specimen 2-4 weeks later should be considered if initial tests are negative but clinical suspicion remains high 1
- Low-level positive viral loads (<5,000 copies/mL) outside the acute infection setting may represent false positives and should prompt retesting of a second specimen 1
- If NAAT is used to diagnose acute HIV-1 infection, document subsequent HIV-1 seroconversion by conventional serologic testing 1
- Fourth-generation assays detect p24 antigen and can identify some but not all cases of acute infection—they miss approximately 27-36% of acute infections that NAT would detect 2, 3