Doxycycline postexposure prophylaxis for sexually transmitted infections: A systematic review and meta-analysis with trial sequential analysis.

ObjectivesTo evaluate the efficacy of doxycycline postexposure prophylaxis (DoxyPEP) for preventing bacterial sexually transmitted infections (STIs) and determine, using trial sequential analysis (TSA), whether the accumulated evidence was sufficient to support reliable conclusions.MethodsIn this systematic review and meta-analysis, we searched four databases through July 29, 2025, for randomized controlled trials (RCTs) comparing DoxyPEP with standard care in men who have sex with men (MSM) and transgender women (TGW) at high STI risk. Random-effects meta-analysis, RoB 2, and TSA were applied (OSF: z8ah6).ResultsThree RCTs involving 1278 participants were included. DoxyPEP reduced any bacterial STI overall (pooled relative risk [RR] 0.41, 95% TSA-adjusted confidence interval [CI] 0.20-0.85), chlamydia (RR 0.22, 95% TSA-adjusted CI 0.12-0.39), syphilis (RR 0.24, 95% TSA-adjusted CI 0.13-0.44), and gonorrhea (RR 0.79, 95% TSA-adjusted CI 0.66-0.95). Pathogen-specific analyzes crossed monitoring boundaries and reached the required information size. The composite crossed the boundary but not its heterogeneity-adjusted required information size (1278/1696); heterogeneity was substantial (I² = 89.1%).ConclusionIn high-risk MSM and TGW, DoxyPEP reduced chlamydia and syphilis, with a smaller gonorrhea benefit. TSA supported the direction of pathogen-specific effects, while the composite estimate and long-term antimicrobial resistance remained uncertain.