Doxycycline pre-exposure prophylaxis (doxyPrEP) versus doxycycline post-exposure prophylaxis (doxyPEP) for preventing bacterial sexually transmitted infections in gay, bisexual, and other men who have sex with men (GBM) and transgender women: protocol for a randomized non-inferiority trial

The global incidence of bacterial sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia, is rising at an unprecedented rate. This trend is particularly concerning among gay, bisexual, and other men who have sex with men (GBM) and transgender women, who experience disproportionately high rates of infection. Despite ongoing public health efforts (e.g. condoms), bacterial STI rates continue to increase, signaling an urgent need for new prevention strategies. Doxycycline prophylaxis has shown potential for STI prevention, with two primary strategies under investigation: post-exposure prophylaxis (doxyPEP), taken within 72 h of condomless sex, and pre-exposure prophylaxis (doxyPrEP), generally taken daily. Early studies suggest doxyPEP significantly reduces bacterial STIs, but data on doxyPrEP remains limited. These two strategies have never been directly compared in a head-to-head trial, leaving a crucial gap in understanding their relative efficacy. The Doxycycline Intervention for STI Chemoprophylaxis (DISCO) study is a prospective, multicentre, open-label, non-inferiority randomized controlled trial (RCT) comparing doxyPrEP (100 mg daily) versus doxyPEP (200 mg after exposure, within 72 h) for the prevention of bacterial STIs among GBM and transgender women. Participants are recruited from Canadian clinical sites in Vancouver, Calgary, Toronto, Hamilton, Ottawa, and Montreal, and followed for 60 weeks. The primary objective is to establish the non-inferiority of doxyPrEP versus doxyPEP in preventing incident bacterial STIs (syphilis, gonorrhea, and/or chlamydia). Secondary objectives include evaluating the frequency of bacterial STIs, treatment adherence, tolerability, safety, changes in sexual behaviour, and antimicrobial resistance (AMR) profiles among participants. This study is the first clinical trial to directly compare doxyPrEP and doxyPEP, addressing the gaps in current evidence. The results will provide critical insights into the efficacy, safety, and AMR implications of these interventions and inform best practices for STI prevention among high-risk populations. The findings have the potential to identify the optimal strategy for reducing the burden of bacterial STIs while minimizing the risks of AMR and associated complications. Clinicaltrials.gov, NCT04762134. Registered 02 February 2021, https://clinicaltrials.gov/study/NCT04762134 .