World Health Organization-Recommended Periodic Presumptive Treatment Versus Doxycycline Post-Exposure Prophylaxis for Sexually Transmitted Infection Control Among Men Who Have Sex With Men in Kenya: Protocol for a Randomized Controlled Trial.

backgroundMen who have sex with men (MSM) are at high risk for bacterial sexually transmitted infections (STIs), including gonorrhea, chlamydia, and syphilis, in Kenya. Because nucleic acid amplification testing (NAAT) is not widely accessible, most gonorrhea and chlamydia infections go undiagnosed and are treated only if symptomatic. World Health Organization (WHO)-recommended periodic presumptive treatment (PPT) and doxycycline post-exposure prophylaxis (doxyPEP) are both potential interventions to reduce the burden of bacterial STIs in this population. Neither has been rigorously tested among MSM in Africa.

objectiveThis study aims to evaluate the effectiveness of WHO-recommended PPT versus doxyPEP, compared with standard syndromic treatment, in reducing the prevalence of bacterial STIs, including gonorrhea, chlamydia, and syphilis, among MSM in Kenya.

methodsWe are conducting an open-label randomized controlled trial with 2900 participants assigned in a 2:2:1 ratio to WHO-recommended PPT given every 3 months, doxyPEP taken 24-72 hours after condomless sex, or standard treatment. Sociodemographic, psychosocial, and behavioral data are collected by audio computer-assisted self-interview. Syphilis testing and treatment are provided as part of standard care. Throat and rectal swabs and urine are collected, pooled, and batch tested for gonorrhea and chlamydia by NAAT; these results are not used to guide treatment. The primary trial outcome is the combined prevalence of laboratory-diagnosed gonorrhea, chlamydia, and early syphilis after baseline; secondary outcomes include the prevalence of each pathogen individually and antimicrobial resistance in Neisseria gonorrhoeae. Primary and secondary outcomes will be compared between each intervention and the common control arm by estimating relative risks over follow-up (months 3-18) using a modified Poisson model fitted with generalized estimating equations. We will also assess implementation outcomes, including acceptability, feasibility, and safety of each intervention compared to standard care among providers and patients using a mixed methods approach. Finally, we will evaluate the potential health and economic impact of scaling up WHO-recommended PPT and doxyPEP compared to standard of care on STI control among MSM and their partners in Kenya using a stochastic, network-based model and cost-effectiveness analysis on trial data.

resultsEnrollment commenced on October 29, 2025. As of November 25, 2025, a total of 357 participants (12.3% of target) have been enrolled, including 133 in Kisumu, 122 in Nairobi, and 102 in Mombasa. Full enrollment is expected to take 6 months, with follow-up occurring over 18 months per participant. Results will be published in 2028.

conclusionsResults of this trial will provide critical data needed to inform guidelines to improve STI control among MSM in sub-Saharan Africa and other resource-limited settings where NAAT is not routinely available. Modeled estimates of the health and economic impact of scaling up these two interventions on STI control among MSM and their partners in Kenya will provide critical information to guide policymakers considering adoption of either intervention.

trial registrationClinicalTrials.gov NCT06468462; https://clinicaltrials.gov/ct2/show/NCT06468462. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/81113.