People who currently or very recently had a positive SARS-CoV-2 PCR test were more likely than those without the COVID-19 virus to get a false-positive result from a fourth-generation HIV-1/2 antigen/antibody assay, U.S. research has found.

About This Study

Increase in False Positive Fourth Generation HIV Tests in Patients with COVID-19 Disease” was published online on May 9, 2023, in Clinical Infectious Diseases. The lead author is Smitha Gudipati, M.D., of the Divisions of Infectious Disease and of Pathology at Henry Ford Hospital in Detroit, Michigan.

Key Research Findings

This retrospective, cross-sectional, single-site study assessed the likelihood of a false-positive HIV test in people with and without a current or very recent SARS-CoV-2 infection. Researchers analyzed the medical records of 31,910 people who had a fourth-generation HIV-1/2 antigen/antibody assay within two weeks of a PCR test for SARS-CoV-2. Most participants had not been vaccinated against COVID-19. The time period for the study spanned from March 2020 to January 2022, thus including both the initial U.S. outbreak and the rollout of multiple rounds of vaccinations.

Overall, 3,613 participants tested positive for SARS-CoV-2; 17 had a false-positive HIV test result, while 19 participants were confirmed to have acquired HIV. Among the 28,297 participants who tested negative for SARS-CoV-2, 70 participants had a false-positive HIV test while 229 participants were confirmed to have acquired HIV.

Among participants with COVID-19, the odds ratio for a false-positive HIV test was 4.22 overall—4.07 when pregnant people were excluded. Most participants with COVID-19 were Black (though the specific proportions varied widely between the study groups), as were 82% of participants without COVID-19 who acquired HIV.
Among participants with false-positive HIV tests, cutoff indices for antigens were significantly higher in those with COVID-19 than those without the respiratory virus. The HIV assays in 10 of 16 available samples among participants with COVID had antigens ≥ 1 and antibodies < 1, compared to none of 11 samples from COVID-negative participants.

Discussion Highlights and Implications for Practice

Results complemented those in an Argentinian study published earlier this year among people who previously had COVID-19.

In the current study, the discrepancy between HIV antigens and antibodies among participants with SARS-CoV-2 suggests that a person’s COVID-19 response produces a protein or peptide that is very similar to HIV’s p24 protein, thereby “confusing” the assay, the study authors stated. Until additional research is conducted, providers should consider COVID-19 a possible cause of an initial positive HIV test they wrote.

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