by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

September 12, 2023

Featured Literature:

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.

Author’s Commentary:

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.

View archived Clinical Research Update entries here.