Population-level impact of doxycycline post-exposure prophylaxis on bacterial sexually transmitted infections

Bacterial sexually transmitted infections (STIs) continue to increase in many high-income settings, disproportionately affecting gay and bisexual men (GBM). Doxycycline post-exposure prophylaxis (doxyPEP) is a highly efficacious strategy for preventing syphilis and chlamydia; however, its population-level impact following national implementation remains uncertain. Australia released an interim position statement in April 2023 and national guidance in September 2023 recommending the consideration of doxyPEP for GBM at increased risk of STIs. Here we analyse sentinel surveillance data from 29 Australian sexual health and general practice services between January 2022 and December 2025. Using interrupted time-series analyses, we examined trends in infectious syphilis, chlamydia and gonorrhoea diagnoses among 78,560 GBM before and after dissemination of doxyPEP trial evidence and national guidance. Observed cumulative STI diagnoses after September 2023 were compared with counterfactual projections based on continuation of preguidance trends. During the 27 months following release of national doxyPEP guidance, cumulative syphilis diagnoses were 55% lower than expected under the counterfactual scenario (rate ratio (RR) 0.45; 95% confidence interval (CI) 0.35 to 0.55), and chlamydia diagnoses were 36% lower (RR 0.64; 95% CI 0.45 to 0.84). No significant change was observed for gonorrhoea (RR 1.11; 95% CI 0.59 to 1.63). These findings provide the first country-level evidence that doxyPEP guidance was associated with sustained reductions in syphilis and chlamydia diagnoses among GBM.