The Relationship Between HIV Preexposure Prophylaxis Use and Laboratory-Confirmed Bacterial Sexually Transmitted Infection Positivity Among a Diverse, Multi-City Cohort of Sexually Active Sexual and Gender Minorities in the United States

The presence of chlamydia, gonorrhea, or syphilis infection is a significant risk factor for HIV acquisition and transmission and disproportionately impacts men who have sex with men (MSM) and transgender women. While HIV preexposure prophylaxis (PrEP) reduces HIV risk, its use may influence sexual behaviors, potentially increasing sexually transmitted infection (STI) exposure. Conversely, PrEP users are often more engaged in care, regularly screened and treated for STIs, and may access other prevention tools such as doxycycline postexposure prophylaxis. Studies on the relationship between PrEP use and STIs have shown mixed results. This cross-sectional analysis included 392 participants (381 cisgender MSM; 11 transgender women) enrolled in the US-based Multicenter AIDS Cohort Study/WIHS Combined Cohort Study between 2021 and 2024 who were sexually active in the year prior to STI testing and HIV negative at their most recent study visit. We assessed whether bacterial STI positivity (i.e., laboratory-confirmed chlamydia and gonorrhea at the urethral, pharyngeal, and/or rectal sites and/or current/past syphilis infection) differed by current PrEP use (yes/no). Multi-variable logistic regression models included sociodemographic and behavioral covariates that were associated with bacterial STI positivity at <i>p</i> < 0.05, with the most parsimonious models selected based on the lowest Akaike Information Criterion. Overall, 32.7% reported current PrEP use. Syphilis was the most prevalent STI (6.8%), followed by chlamydia (3.2%) and gonorrhea (2.1%); 11.7% of PrEP users tested positive for at least one STI, compared with 6.1% of non-PrEP users. Among PrEP users, 37.9% reported stopping or decreasing condom use, and 31.6% reported an increased number of sex partners after initiating PrEP. In both bivariate and multi-variable models, PrEP use was associated with higher odds of gonorrhea positivity (adjusted odds ratio = 4.70, 95% confidence interval [CI]: 1.10-20.04, <i>p</i> = 0.037) and greater odds of being positive for at least one STI (crude odds ratio = 1.94, 95% CI: 1.06-3.90, <i>p</i> = 0.041). No significant differences were observed for chlamydia and syphilis by PrEP use status. Overall, these findings suggest that current PrEP users (vs. non-PrEP users) have an increased odds of bacterial STI positivity, particularly gonorrhea, in a diverse, multi-city cohort of HIV negative, sexually active MSM and transgender women in the United States PrEP remains highly effective in preventing HIV, and our results underscore the importance of integrated sexual health services that support ongoing STI screening and prevention alongside PrEP use among sexual and gender minorities.