by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
September 12, 2023
Gudipati S, Shallal A, Peterson E, Cook B, Markowitz N. Increase in false-positive fourth-generation Human Immunodeficiency Virus Tests in Patients with Coronavirus Disease 2019. Clin Infect Dis. 2023 Aug 22; 77(4):615-619. doi: 10.1093/cid/ciad264. PMID: 37158382
This retrospective, cross-sectional study from a single urban tertiary care hospital examined electronic health records of patients with SARS-CoV-2 PCR results within two weeks of a laboratory-based HIV fourth-generation assay (March 2020 to January 2022). All positive fourth-generation assays were independently reviewed and categorized as a false positive; true positive; or presumptive negative. A total of 31,910 records met eligibility criteria: 31,575 presumptive negative results, 248 true positives, and 87 false positives. After adjustment for age, sex, race, ethnicity, pregnancy, and SARS-CoV-2 immunization status, only false positive HIV test results were significantly associated with COVID-19. Repeat analyses after removing pregnancy as a covariate revealed similar findings. A false positive HIV result was 2.93 more likely to occur in those with COVID-19 versus those without COVID-19. Available signal-to-cutoff indices were analyzed for 256 patients. False positive results were associated with the Ag portion of the HIV assay in 87.1% vs. 33.9% for the Ab portion. Additionally, false positive cut-off indices for the Ag portion of the assay were significantly greater in magnitude among people with COVID-19 infection versus people without COVID-19. False positive results due to the Ab portion were less commonly seen in people with COVID-19 infection, but the magnitude of the cut-off indices in these results were not different.
Although multiple case reports of false positive HIV tests related to COVID-19 have been published over the last few years, this study is one of few that has tried to determine the false positive rate across a particular population. Further, the detailed analysis of signal to cut-off ratios and individual chart review of all false positive cases is notable. Authors offer antigenic homology as a potential explanation for their findings, and also note some limitations including the fact that only one platform for HIV and COVID-19 testing was used. Nevertheless, their conclusion that acute COVID-19 should be considered as a potential explanation for false positive HIV screens (including fourth-generation Ag/Ab assays) is sound. For communities experiencing increases in COVID infection, these findings should be kept in mind when reviewing HIV screening results, especially if reactive results were unanticipated. Importantly – providers should remain aware of the significant implications of false positive HIV results in certain scenarios such as pregnancy, as illustrated by this case report.
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