A COMPLETED study of doxycycline used after condomless sex has shown significant reductions in bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. The trial, known as DoxyPEP, included participants in Seattle, Washington, and San Francisco, California, who had at least one STI in the prior year.
In the study, 637 participants were enrolled and randomly assigned to either standard care or a post-exposure prophylaxis strategy using doxycycline. Those in the treatment group took a 200 mg dose of doxycycline within 24 to 72 hours after condomless sex. The main goal was to assess whether this approach could lower the quarterly incidence of bacterial STIs, specifically chlamydia, gonorrhoea, and syphilis.
Among the 592 participants who completed at least one follow-up quarter during the randomised phase, the STI incidence rate was 12% in the doxycycline group, compared to 30.5% in the standard care group. This translates to a 61% relative reduction in bacterial STIs, a statistically significant finding. After the randomised phase was stopped early due to clear benefits, remaining participants were offered doxycycline in an open-label extension. STI rates remained low in both those who continued and those who initiated the regimen during this phase.
Safety outcomes were encouraging. Only one Grade 2 lab abnormality and five Grade 3 adverse events were possibly or probably related to doxycycline use. There were no serious adverse events linked to the treatment. Regarding antibiotic resistance, of those who developed gonorrhoea during the study, the proportion with tetracycline-resistant strains was similar whether they were taking doxycycline or not.
Researchers concluded that doxycycline post-exposure prophylaxis is an effective strategy for preventing bacterial STIs in high-risk populations. The treatment was well tolerated and remained effective even after participants knew they were receiving it. These findings could support wider use of this approach in sexual health programmes, while ongoing monitoring for antibiotic resistance remains important.
Reference
Luetkemeyer AF et al. Doxycycline to prevent bacterial sexually transmitted infections in the USA: final results from the DoxyPEP multicentre, open-label, randomised controlled trial and open-label extension. Lancet Infect Dis. 2025; DOI: 10.1016/S1473-3099(25)00085-4.
