Background
Doxycycline post-exposure prophylaxis (DoxyPEP) prevents bacterial STIs in trials, but real-world effectiveness and safety signals remain uncertain.
Methods
We reviewed people presenting to a community sexual health clinic in Providence, Rhode Island from May 2023 to July 2025. We summarized demographics and DoxyPEP awareness and uptake, as well as modeled encounter-level associations between time-varying current DoxyPEP use (past 30 days) and time-varying chlamydia, gonorrhea, and syphilis using mixed-effects logistic regression with random intercepts for people (exact logistic for sparse syphilis). Significance was defined as p<0.05.
Results
Among 1,577 unique adults (median age 31 [IQR 26–38]), 22% identified as Black/African American, 22% Hispanic/Latino, 16% transgender/gender-diverse/nonbinary, and 2.4% were living with HIV (PLWH). Sixty-two percent of people had heard of DoxyPEP and 30% reported ever using. DoxyPEP uptake did not differ by race/ethnicity or insurance. Each year of age was associated with 2% higher odds of ever using DoxyPEP (OR 1.02, 95% CI 1.01–1.03). Compared with cisgender men, cisgender women were less likely to report ever use (OR 0.18, 95% CI 0.12–0.25) and transgender/gender-diverse individuals were also less likely (OR 0.36, 95% CI 0.27–0.48); PLWH had higher odds of use (OR 2.92, 95% CI 1.46–5.85). In mixed-effects models adjusted for age and gender identity, DoxyPEP use in the last 30 days was associated with 67% reduction in chlamydia (aOR 0.33, 95% CI 0.12–0.92). For gonorrhea, DoxyPEP use was associated with higher odds in HIV-negative people (OR 2.29, 95% CI 1.47–3.56) and PLWH (OR 15.85, 95% CI 1.81–138.44). For syphilis, exact logistic regression showed no significant association (median-unbiased OR 0.64; exact 95% CI 0–4.07), consistent with low event rates.
Conclusions
In this real-world setting, DoxyPEP awareness and uptake were substantial and highest among cisgender men and PLWH. Current DoxyPEP use was linked to lower chlamydia diagnoses, higher gonorrhea rates, and no clear benefit in syphilis prevention. Ongoing surveillance is warranted to monitor real-world effectiveness and potential unintended consequences of DoxyPEP.