Can a 4th generation (4th gen) and qualitative Polymerase Chain Reaction (PCR) test result turn positive at day 90 after initially being negative at 83 days?

From the Guidelines

Yes, a 4th generation HIV test and qualitative PCR test can potentially turn positive at day 90 after being negative at day 83. This scenario, although uncommon, can occur due to several factors such as delayed seroconversion, viral load fluctuations, laboratory variability in test sensitivity, or a very recent infection where viral markers are just becoming detectable 1. The 4th generation test detects both HIV antibodies and p24 antigen, while PCR tests detect viral genetic material.

Key considerations in this context include:

• Delayed seroconversion, where the immune response develops more slowly than typical
• Viral load fluctuations, where levels temporarily drop below detection limits
• Laboratory variability in test sensitivity
• A very recent infection, where viral markers are just becoming detectable

Given these factors, follow-up testing is essential to confirm results, especially when there's clinical suspicion of HIV infection. Healthcare providers typically recommend retesting after the window period (usually 45-90 days post-exposure) to ensure accuracy, as highlighted in guidelines for antiretroviral drugs for treatment and prevention of HIV infection in adults 1. This situation underscores why single negative tests during the window period aren't definitive and why follow-up testing is crucial for conclusive results.

From the Research

PCR Test Results

• The provided studies do not directly address the question of whether a 4th generation and qualitative PCR test result can turn positive at day 90 after initially being negative at 83 days.
• However, a study on SARS-CoV-2 RT-PCR testing 2 found that among initially negative patients who were re-tested within 7 days, 3.5% yielded a positive result, suggesting that false negative results can occur.
• Another study on the effectiveness of routine asymptomatic PCR testing 3 estimated that the probability of detecting an infection peaks at 77% 4 days after infection and decreases to 50% by 10 days after infection.

Virus Detection and PCR Testing

• A study on viral load and burden modification following early antiretroviral therapy of primary HIV-1 infection 4 found that early HAART led to a rapid reduction in HIV-RNA to undetectable levels, but HIV-DNA remained detectable at low levels.
• A study on circulating HIV-1-infected cell burden from seroconversion to AIDS 5 found that the infected cell burden was relatively stable within each subject after seroconversion, but varied greatly among subjects.
• A study on the occurrence and timing of subsequent SARS-CoV-2 RT-PCR positivity among initially negative patients 2 found that the majority of patients with an initial negative result who warranted reevaluation for any reason remained negative on all subsequent tests performed within a 7-day window.

Limitations and Considerations

• The provided studies have limitations, such as the inability to control for unmeasured confounders in observational studies 6.
• The studies also have different focuses, such as the effectiveness of routine asymptomatic PCR testing 3, the occurrence of subsequent SARS-CoV-2 RT-PCR positivity 2, and the viral load and burden modification following early antiretroviral therapy 4.