The Hidden Problem of Cross-Reactivity: Challenges in HIV Testing During the COVID-19 Era: A Systematic Review

Introduction Human immunodeficiency virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) surface glycoproteins, including shared epitope motifs, show similarities. This may lead to false-positive HIV results due to cross-reactivity between the two viruses. This study presents a systematic review of the published studies on their cross-reactivity. Methods A systematic review of the published studies of HIV and SARS-CoV2 cross-reactivity was conducted, the studies that met the following criteria were included: 1) Studies in the English language. 2) Studies in which the title included the required keywords. 3) Studies in which false positive results were achieved and confirmed. 4) Studies investigating the possibility of cross-reactivity between HIV and SARS-CoV2. Results A total of 11 studies and 466,140 patients were analyzed. Of the specified sexes, 363,786 (82.1%) of the participants were males. A total of 707 false-positive HIV results were recorded, of which 122 (17.3%) had detectable Coronavirus disease 2019 (COVID-19) antibodies. The remaining 585 (82.7%) false positives were either healthy patients or patients recovered from COVID-19 with no detectable COVID-19 antibodies. Twenty-five distinct tests were used as initial and confirmatory tests for both COVID-19 and HIV. Six (24%) unique fourth-generation HIV antigen/antibody combination tests, six (24%) HIV-specific molecular tests, and four (16%) HIV immunoassays were used. Conclusion COVID-19 should be considered a potential cause of false-positive results in HIV tests, due to the cross-reactivity between the antibodies or antigens from both viruses.