Recent COVID-19 can confound HIV test results

Testing for HIV-1 during or shortly after COVID-19 is a common scenario; however, the effect of SARS-CoV-2 infection on the accuracy of HIV screening has not been formally assessed. Investigators in Detroit retrospectively examined HIV antigen/antibody (fourth generation or combo) assay results in persons who also underwent a PCR test for SARS-CoV-2 within the next 2 weeks. HIV testing consisted of a combo test with a follow-up PCR test for HIV RNA to differentiate between true-positive (TP) and false-positive (FP) results. To determine the contribution of HIV antigen versus antibody in a positive screening test, cut-off indexes were analyzed for the two measures from the combo test.

About 32,000 records from March 2020 to January 2022 met eligibility criteria. Of these, 335 showed a positive HIV combo test (74% TP and 26% FP). Rates of SARS-CoV-2 positivity by HIV status were 7.7% (TP), 19.5% (FP), and 11.3% (HIV negative). In the TP group, a positive combo test was associated solely with antibody reactivity most often (87.1%), whereas combo positivity was based exclusively on antigen reactivity 66.1% of the time (p<0.001) in the FP group. After adjustment for covariates such as age, race, sex, pregnancy, and SARS-CoV-2 vaccination, only SARS-CoV-2 PCR positivity was significantly associated with a FP HIV test result (over three-fold excess risk).

Comment

The observation that 26% of positive HIV combo tests were false positive in the setting of active COVID-19 is striking and warrants confirmation. The authors discuss the similarities between HIV-1 and SARS-CoV-2 proteins, suggesting cross-reactivity as a possible mechanism for their findings, thereby providing direction for follow-up studies. In the meantime, clinicians should be aware of this association, which provides further rationale for routine follow-up HIV RNA testing after a positive HIV combo test.

Citations

Gudipati S et al. Increase in false positive fourth generation HIV tests in patients with COVID-19 disease. Clin Infect Dis 2023 May 9; [e-pub]. (https://doi.org/10.1093/cid/ciad264. opens in new tab)