A variety of infections and inflammatory conditions have been associated with false positive (FP) serological tests, including those for HIV. In the context of an HIV counseling, testing, and referral program, an apparent increase in FP 4th generation HIV tests was observed among persons infected with SARS-CoV-2. We sought to determine if there was an association of active coronavirus disease-2019 (COVID-19) with a FP HIV test.
This was a retrospective, cross-sectional study from March 2020 to August 2021 at Henry Ford Hospital. Through electronic medical record extraction, all results for SARS-CoV-2 by PCR within + two weeks of a diagnostic HIV 4th generation assay (Elecsys HIV Duo, Roche Diagnostics, Indianapolis, IN) were selected. Confirmatory HIV-1 and HIV-2 antibodies, as well as quantitative HIV RNA, was performed for all positive 4th generation tests. All positive HIV 4th generation assays were independently reviewed and divided into groups of FP, true positives (TP), and true negatives (TN). Variables included age, race, ethnicity, and sex. Statistical analysis was performed in a pairwise fashion using a Chi-squared test. Multivariate logistic regression was used to predict positive COVID-19 tests.
A total of 23,278 medical records meeting the above criteria were reviewed. The rates of COVID positive tests were then arranged in groups of HIV TP, FP, and TN. In total, 23,041 patients had a TN HIV test result, 167 patients had a TP, and 70 patients had a FP (Table 1). Those with HIV FP tests had the highest percentage of COVID positive test results at 22.9% (p=0.001), which was significantly higher than HIV TN (10.2%; p=0.197) and HIV TP (7.2%; p=0.001). After adjustment for all covariates, only FP HIV was significantly associated with COVID-19 (OR=7.04; p=0.001).
This study reveals that patients with active COVID-19 disease are significantly more likely to have a false positive 4th generation HIV test. The mechanism for this is unknown but may reflect broad polyclonal antibody generation in acute infections or cross-reactivity to antibodies with the SARS-CoV-2 spike protein. Although only a single 4th generation test was evaluated in this study, acute COVID-19 infection should be considered as a potential etiology for a false positive 4th generation HIV test.