Background
DoxyPEP has high prevention efficacy for sexually transmitted infections (STI) among cisgender men and transgender people. Previous work from Magnet Sexual Health Clinic at San Francisco AIDS Foundation (Magnet) found that only 61% of DoxyPEP users reported using the medication consistently within 72 hours of sexual exposures. The STI risk reduction of DoxyPEP may be affected by actual levels of use among those with the medication. Therefore, we sought to assess risk of STI associated with self-reported high adherence among DoxyPEP users.
Methods
We used client data from Magnet visits from 09/2023-08/2025. We included visits where clients were tested for at least 1 STI and self-reported whether they used DoxyPEP in the past 3 months. We constructed Poisson log regression models using generalized estimating equations with robust standard errors accounting for participant clustering to estimate relative risks (RR) of incident syphilis, gonorrhea, and chlamydia in two models of DoxyPEP use: (1) any self-reported current use of DoxyPEP among all Magnet clients and (2) DoxyPEP adherence in the past 3 months, measured as self-report of always using DoxyPEP within 72 hours of a sexual encounter, among current DoxyPEP users. We adjusted for number of sexual partners and housing stability.
Results
We included in the study 22,286 visits among 8,188 unique clients. Overall, 3,512 (43%) reported currently using DoxyPEP at their most recent visit and 1,693 (48%) of those clients reported always using DoxyPEP as directed since their last visit. In models with any current use of DoxyPEP as the independent variable, the risks of syphilis (aRR=0.44 [95% CI: 0.22, 0.84]) and chlamydia (aRR=0.40 [0.30, 0.53]) were significantly lower; however risk of gonorrhea was higher (aRR=1.17 [1.00, 1.37], p = 0.047). In models assessing self-reported high adherence of DoxyPEP, the risk of gonorrhea (aRR=0.79 [0.68, 0.91]) and chlamydia (aRR=0.47 [0.31, 0.70]) were lower, but the risk of syphilis was not (aRR=0.71 [0.29, 1.71]).
Conclusions
Our findings that any DoxyPEP use is associated with a lower risk of syphilis and chlamydia is consistent with clinical trial and implementation results. The lower risk of gonorrhea and chlamydia associated with self-reported high adherence among DoxyPEP users suggests that high DoxyPEP adherence plays a key role in STI transmission dynamics. Future studies on the effectiveness of DoxyPEP should include measures of adherence to better contextualize its impact on STIs incidence