1. Why should you do this study?

We are conducting this study to test two different interventions to improve sexually transmitted infection (STI) control among gay, bisexual, and other men who have sex with men (GBMSM) in Kenya. GBMSM have a high burden of STI that mostly are detected by expensive laborotory tests that are not available in public hospitals.

2. What questions are we trying to answer?

One intervention that may reduce STIs among GBMSM is periodic presumptive treatment (PPT), in which one is treated every 3 months for STI regardless of symptoms. STI PPT has been recommended by the World Health Organization for GBMSM but never tested in a randomized trial. The other intervention is called doxyPEP, which consists of taking a medication called doxycycline 24-72 hours after you have condomless sex, as post-exposure prophylaxis (PEP) to prevent STI. DoxyPEP has been found to reduce STI among GBMSM in the United States and France but has not been tested among GBMSM in sub-Saharan Africa. No one knows if STI PPT or DoxyPEP is better at reducing STI among GBMSM in Kenya and similar settings.

3. Where is the study taking place?

In 3 friendly GBMSM study sites in Kisumu, Nairobi, and Mombasa.

4. How many participants does it involve? We will enroll 2900 GBMSM participants. In addition up to 60 study staff will provide feedback on the two interventions.

5. How will they be selected?

GBMSM participants will be engaged and screened for eligibility at community-based organizations at each of the three study sites. Participants need to be between 18-29 years, report condomless anal intercourse with a man in the past 6 months, multiple partners or a partner with a STI. They need to be willing to follow study procedures and remain in the study area for 18 months. GBMSM will be excluded if they are unable to understand the study purpose and procedures despite a thorough explanation by and discussion with the study team, are allergic to any of the antibiotics used, have used antibiotics for 14 days or more in the month before enrolment, or are taking medications that impact any of the antibiotics used.

6. What does the study involve for those taking part?

Participants will be randomised to one of the following three groups: PPT, doxyPEP or standard of care. They will make seven quarterly research visits during the study, for 18 months from enrolment. At each visit, a clinician will collect 2 throat swabs, 2 rectal swabs, urine, and blood from each participant. Blood will be tested for syphilis and, if there is an infection, participants will be treated according to standard of care as soon as results are available. The swab and urine samples will be tested for gonorrhea and chlamydia at the end of the study, to determine which intervention worked best to reduce STI. At each visit a small hair sample will also be collected to measure antibiotic use in all participants. Additonally, a digital fingerprint will be taken to allow us to confirm partcipant’s identity at study visits without using a name or other identifiers. We will also collect a brief survey lasting 50-60 minutes on a tablet computer. This survey will include questions about sexual behavior, STI symptoms, and bioc use, substance use, and mental health.

7. What are the risks and benefits of taking part?

6 Version 1.1, dated 10 June 2024 There is a small risk of loss of privacy. For participants assigned to the intervention groups there is risk of medication side effects. Participants may benefit from regular physical exams, free syphilis testing, and counselling about STI prevention.

8. How will the study benefit society?

The burden of STI among GBMSM and their sexual partners in Kenya may be reduced through the outcomes of this study. This is a contribution to science and will help inform health policy for GBMSM in Kenya and similar resource-limited settings.

9. When does the study start and finish?

The study will likely start in the second half of 2024 and follow patients over 3 years (through June 2027), followed by testing of samples for chlamydia and gonorrhea and for antibiotic resistance in gonorrhea, as well as modeling and cost-effectiveness evaluations to inform scale-up, should either intervention prove to be more effective than standard care

Men who have sex with men (MSM) are at high risk for gonorrhoea and chlamydia in Kenya, where nucleic acid amplification testing (NAAT) is not feasible, and most infections therefore go undiagnosed. In 2011, the WHO recommended periodic presumptive treatment (PPT) of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections for MSM at high risk for HIV acquisition due to condomless anal intercourse with multiple sex partners or a recent STI exposure. More recently, trials in well-resourced settings have demonstrated the efficacy of doxycycline post-exposure prophylaxis (doxyPEP) for reducing NG, CT, and syphilis infections among high-risk MSM. The goal of this study is to evaluate the impact and cost-effectiveness of WHO-recommended PPT versus doxyPEP compared to standard syndromic treatment among Kenyan MSM. This study aims to (1) evaluate the effectiveness and impact on antimicrobial resistance in NG of WHO-recommended PPT given every 3 months and of doxy-PEP taken 24-72 hours after condomless sex for reducing STI burden among Kenyan MSM; (2) assess the acceptability, feasibility, and safety of implementing WHO-recommended PPT and doxy-PEP compared to standard care among providers and patients; and (3) model the health and economic impact of scaling up WHO-recommended STI PPT and doxyPEP compared to standard of care on STI control among MSM and their partners in Kenya. We will conduct an open-label randomized trial with 2900 participants to evaluate these two interventions versus standard care assigned in a 2:2:1 ratio, with 18 months of follow-up at three MSM-friendly research clinics in Kenya. Results will inform parameters to update a stochastic model of STI transmission and cost-effectiveness analysis to project the impact of scaled-up STI PPT and doxyPEP in Kenya. This work will provide the critical data needed to inform guidelines and improve STI control among this key population in sub-Saharan Africa and other resource-limited settings.