Real-World Clinical Outcomes of Doxycycline Post-Exposure Prophylaxis for Bacterial STI Prevention

Doxycycline post-exposure prophylaxis (DoxyPEP) is effective in preventing bacterial sexually transmitted infections in clinical trials, but real-world effectiveness data are limited.

All patients presenting to a community-based clinic in Providence, Rhode Island, from May 2023 to July 2025 were reviewed. Mixed-effects logistic regression models were used to assess associations between DoxyPEP use (past 30 days) and chlamydia, gonorrhea, and syphilis diagnoses. Significance was defined as P < 0.05.

Among N = 1577 unique adults (median age 31), 22% identified as Black/African American, 22% Hispanic/Latino, 16% transgender/gender-diverse/nonbinary, and 2.4% were people living with HIV (PLWH). Sixty-two percent of people had heard of DoxyPEP and 30% reported ever using it. Each year of age was associated with 2% higher odds of ever using DoxyPEP (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03). PLWH had higher odds of DoxyPEP use (OR: 2.92, 95% CI: 1.46-5.85). DoxyPEP use in the last 30 days was associated with a 67% reduction in chlamydia (adjusted odds ratio: 0.33, 95% CI: 0.12-0.92). For gonorrhea, DoxyPEP use was associated with higher odds of infection in people without human immunodeficiency virus (OR: 2.29, 95% CI: 1.47-3.56) and PLWH (OR: 15.85, 95% CI: 1.81-138.44). For syphilis, there was no significant association (OR: 0.64; 95% CI: 0-4.07), reflecting low numbers of diagnoses.

In this real-world setting, DoxyPEP awareness and uptake were substantial and highest among cisgender men and PLWH. Current DoxyPEP use was associated with fewer chlamydia diagnoses, higher gonorrhea rates, and no clear benefit in syphilis prevention due to low numbers.