Doxycycline for Postexposure Prophylaxis of Sexually Transmitted Infections: A Systematic Review and Meta-analysis

A BSTRACT Background: Sexually transmitted infections (STIs) continue to pose a significant global health challenge, particularly impacting high risk populations such as men who have sex with men (MSM) and transgender women. Doxycycline postexposure prophylaxis (PEP) has emerged as a potential strategy to help reduce STI incidence in these groups. Aims and Objectives: To systematically review and meta analyze effectiveness, safety, acceptability, and antimicrobial resistance (AMR) outcomes associated with doxycycline PEP for STI prevention. Materials and Methods: A comprehensive search of electronic databases (PubMed, Embase, and the Cochrane Library) was performed to identify relevant studies published up to January 31, 2025. Eligible studies included randomized controlled trials (RCTs) and observational studies assessing doxycycline PEP in high risk populations. The primary outcome was the incidence of bacterial STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum). Secondary outcomes included safety, tolerability, acceptability, and anti AMR. A random effects meta analysis was performed to estimate pooled effect sizes. Results: Seven studies (including five RCTs in the meta analysis) involving 3,233 participants met the inclusion criteria. Doxycycline PEP significantly reduced the incidence of bacterial STIs by 54%, compared to standard care or no prophylaxis (pooled effect size: 0.46; 95% confidence interval 0.25–0.84; P = 0.01). The intervention was generally well tolerated, with gastrointestinal symptoms being the most frequently reported adverse events. Acceptability was high, although adherence varied among studies. Evidence regarding AMR was limited and inconsistent. Conclusion: Doxycycline PEP represents a promising approach for preventing bacterial STIs in high risk populations, particularly MSM and transgender women. Its implementation should be accompanied by regular STI testing, treatment, and behavioral interventions, alongside careful monitoring of adherence and AMR.