Daily, Weekly, or Event-driven Doxycycline for STI Prevention Among Men Who Have Sex With Men (MSM) Engaging in Chemsex: The DOSE Non-inferiority Trial (DOSE)

This study will evaluate the acceptability, effectiveness, and adherence of alternative doxycycline dosing strategies to optimize STI prophylaxis in this high-risk population. We will accomplish this through the following independent, yet interrelated Aims: 1) Determine effectiveness of fixed-dose daily, fixed-dose weekly, and event-driven dosing of doxycycline for STI prophylaxis; 2) Assess acceptability and preferences for doxycycline as STI prophylaxis through either fixed dose (daily or weekly) or event-driven (post-exposure) dosing strategies through individual interviews; 3) Evaluate and compare adherence and tolerability of daily, weekly, and event-driven doxycycline dosing strategies. We will conduct an open-label, non-inferior, randomized control trial (RCT) comparing fixed-dose daily, fixed-dose weekly, and event-driven doxycycline dosing strategies on quarterly incidence of STIs among MSM who use MA. We will screen 900 individuals to recruit a cohort of 300 MSM who self-report MA use in conjunction with condomless anal intercourse in the past month. At the Enrollment visit, participants will receive HIV, syphilis, and gonorrhea/chlamydia (GC/CT) testing as well as complete demographic and behavioral questionnaires. Enrolled participants will be randomly assigned 1:1:1 to either fixed-dose daily doxycycline (100mg daily; n=100), fixed-dose weekly doxycycline (200mg weekly; n=100), or event-driven doxyPEP (200mg taken up to 72 hours after a potential STI exposure; n=100; standard of care). All participants will participate in Quarterly follow-up visits where they will be assessed for HIV, bacterial STIs (GC/CT and syphilis), adherence to doxycycline, sexual behaviors/practices, substance use, nasal Staph aureus colonization and doxycycline resistance over 12 months. The primary outcome for this study will be quarterly incidence of, GC, CT, and/or early syphilis (defined as newly positive rapid plasma reagin [RPR] or four-fold rise in RPR titers), by arm.