Efficacy of Doxycycline as Pre-exposure and/or Post-exposure Prophylaxis to Prevent Sexually Transmitted Diseases: A Systematic Review and Meta-analysis

Abstract Introduction Bacterial sexually transmitted infections (STIs), specifically infection by Chlamydia trachomatis , Neisseria gonorrhoeae , and Treponema pallidum , have an important burden worldwide. The use of doxycycline as Pre-Exposure Prophylaxis (PREP or Doxy-PREP) or Post-Exposure Prophylaxis (PEP or Doxy-PEP) might be effective as prophylaxis since it is effective against C. trachomatis and T. pallidum . Aims Our objective was to evaluate the efficacy of doxycycline as PREP or PEP against bacterial STIs ( C. trachomatis , N. gonorrhoeae , and Treponema pallidum ). Methods A systematic review and meta-analysis of randomized clinical trials of a high-risk group of individuals was conducted to evaluate whether doxycycline is as effective as PREP or PEP in preventing bacterial STIs. The PubMed-MEDLINE, Cohrane, Scielo, and LILACS databases were searched for randomized clinical trials published up to March 2024. Data were extracted from published reports. Hazard Ratios (HRs) and Risk Ratios (RR) with 95% CI were pooled across trials. Main outcome measure The primary endpoints were any incidence of bacterial STIs and individual STI infections. Results A total of four studies were included in the analysis, three of which evaluated Doxy-PEP and one evaluated Doxy-PREP. In the Doxy-PEP group, a total of 1182 participants were evaluated. In the pooled analysis of Doxy-PEP studies, the incidence of the first STI was lower in the Doxy-PEP group (HR = 0.538 [95% CI = 0.337-0.859]) (I 2 = 77%; P -value <0.05). Regarding individual infections, only two studies were included. In the Doxy-PEP group, the incidence of individual infection of C. trachomatis was lower compared to controls (RR = 0.291 [95% CI = 0.093-0.911]) (I 2 = 89%; P -value <0.05). Since only one study evaluated Doxy-PREP, it was not possible to calculate a meta-analysis index; however, the use of doxycycline as pre-exposure prophylaxis was associated with a decrease in the rate of any STI. Conclusions The use of Doxy-PEP might reduce the first STI, mainly C. trachomatis , if used within 72 h after condomless sex. The use of Doxy-PREP might also decrease the chance of any STI, however, only one study was evaluated.