• Doxycycline PEP should be provided as part of a comprehensive sexual health approach, complementing other prevention strategies such as condom use.
• Men who have sex with men and transgender women with recent or recurrent STIs – especially syphilis – and those in high-incidence sexual networks or settings should be given priority.
• Context-appropriate monitoring of antimicrobial resistance is strongly encouraged as part of doxycycline PEP policy. Ideally, trends in both antimicrobial resistance and antibiotic use should be monitored.

Timing of doxycycline use

* Doxycycline should be taken as PEP ideally within 24 hours, and no later than 72 hours, after condomless sex to maximize effectiveness. This timing interval is based on trial protocols and reflects doxycycline’s pharmacological profile, including differences in drug distribution across different mucosal tissues. * Use is event-driven—based on exposure—and repeat 200-mg dosing within any 24-hour period should be avoided to reduce the risk of adverse events given the drug’s long half-life. Depending on the frequency of use, some people may effectively transition along a continuum between doxycycline PEP and PrEP. There is currently no evidence to support daily use, and WHO does not currently recommend doxycycline for PrEP, but future guidance may be developed as more evidence becomes available. * Continued monitoring of adverse events and communicating approaches to mitigating side effects (such as taking doxycycline with food to reduce gastrointestinal discomfort) are important. Nutrient interactions should be considered: products containing iron, magnesium, or calcium—including supplements and dairy foods—can reduce doxycycline absorption and should be taken at least a few hours apart from doxycycline.

Setting priorities based on STI risk

* Men who have sex with men and transgender women, and men who have sex with men with recent STIs—especially syphilis—and those in high-incidence sexual networks or settings should be given priority because the preventive effect of doxycycline PEP is most powerful for these populations. High-incidence networks or settings are environments or groups of people in which STIs are circulating at higher than usual levels, increasing the likelihood of exposure because more partners, or partners’ partners, are infected. * Eligibility should be periodically reassessed, considering changes in STI incidence, sexual behaviour, individual preferences, and medication tolerance, to support person-centred care and antimicrobial stewardship. * Cost-effectiveness improves and unnecessary antibiotic use is limited when people with a higher incidence of infection are targeted for doxycycline PEP. Broad, general population-level roll-out of doxycycline PEP without assessing individual STI risk behaviour should be avoided.

Integration into comprehensive health services

* Doxycycline PEP should be integrated into a comprehensive prevention and sexual health approach rather than being offered as a stand-alone intervention. It can complement—but does not replace—other prevention strategies such as condoms, STI testing, and partner services. * Messaging for demand creation should focus on pleasure and empowerment and be non-stigmatizing. Lessons from HIV PrEP implementation highlight the importance of community engagement, peer-led education, and outreach in this process. * Educational materials are important for informed decision-making. Other key elements for high-quality integrated service provision include access to counselling, non-judgemental STI prevention, testing and treatment, and linkage to HIV prevention and treatment services as appropriate.

Service delivery models for equitable access

* Locally appropriate service pathways for doxycycline PEP are essential for equitable access, especially if these can ensure low-cost access. These could include primary health care facilities, sexual health clinics, and community-based services. Provision through pharmacies (with and without prescription) and online platforms, as guided by local laws and regulations, may provide additional options. * Task-sharing of prescription, provision, and/or dispensing to lay providers, and clarification of prescription terms, are important to ensure scalability in low-resource and diverse settings.