False-Positive Screening and Confirmatory HIV Diagnostic Test in a Patient with Cured SARS-CoV-2 Infection Is Not Mediated by Env/Spike Cross-Reactive Antibodies

Abstract

Acute SARS-CoV-2 infection has been associated with false-positive HIV screening tests. The underlying mechanism is unclear, and for clinical cases, evidence beyond a temporal connection is missing. However, several experimental studies point toward SARS-CoV-2 spike/HIV-1 envelope (Env) cross-reactive antibodies (Abs) as a cause. Here, we present the first case of an individual with convalescent SARS-CoV-2 infection testing false positive in both an HIV screening and confirmatory test. Longitudinal sampling showed that the phenomenon was temporary but lasted for at least 3 months before waning. After excluding a multitude of common determinants for assay interference, we further show by antibody depletion studies that SARS-CoV-2-spike-specific Abs did not cross-react with HIV-1 gp120 in the patient sample. No additional case of HIV test interference was identified in a cohort of 66 individuals who presented to a post-COVID-19 outpatient clinic. We conclude the SARS-CoV-2-associated HIV test interference to be a temporary process capable of disturbing both screening and confirmatory assays. The assay interference is short-lived and/or rare but should be considered by physicians as a possible explanation for unexpected HIV diagnostic results in patients with a recent SARS-CoV-2 infection.