Sheng Feng, Shivakumar Narayanan, Mengjie Li, Hui Chen, Kristie Johnson, Robert H Christenson
False-reactive HIV Ag/Ab screening results increased during the pandemic and remained elevated afterward. Associated factors analysis and S/CO distributions may help interpretation of questionable reactive screens. Our findings reinforce the importance of reflex HIV nucleic acid testing (NAT) for discordant results.
OBJECTIVE: False-reactive results of the fourth-generation HIV-1/2 antigen/antibody (Ag/Ab) Combo assay trigger additional testing, increased costs, and patient anxiety. Large-scale analyses of false-reactive results spanning the COVID-19 pandemic in high-prevalence communities are lacking. This study aims to investigate the frequency of false-reactive HIV-1/2 Ag/Ab Combo screening results before, during, and after the COVID-19 pandemic and to identify associated patient factors.
DESIGN: We conducted a retrospective study of HIV-1/2 Ag/Ab Combo assays performed from 2019 to 2024 at a tertiary care medical center in Baltimore, MD. False-reactive proportions were compared across pre-pandemic (January - December 2019; n = 12,347), pandemic (January 2020 - June 2023, n = 33,546), and post-pandemic (July 2023 - December 2024; n = 12,238). Associations between false-reactive results and selected patient factors were assessed.
RESULTS: Among 58,131 screens, 1236 (2.1%) were reactive; 185 were false-reactive, yielding a false-reactive proportion of 15.0% among reactive results. The false-reactive proportion increased from 5% pre-pandemic to 17.9% at the onset of the COVID-19 pandemic and remained near 20% during the pandemic, declining to approximately 14% by 2024 post-pandemic. In multivariable analysis, age > 65 or < 21, White race, and American Indian/Alaska Native race were associated with higher odds of false-reactive results, whereas coinfection of syphilis was associated with lower odds. Most false-reactive results clustered at low signal-to-cutoff ratio (S/CO) values.
CONCLUSIONS: False-reactive HIV Ag/Ab screening results increased during the pandemic and remained elevated afterward. Associated factors analysis and S/CO distributions may help interpretation of questionable reactive screens. Our findings reinforce the importance of reflex HIV nucleic acid testing (NAT) for discordant results.