Impact and cost-effectiveness of doxycycline post-exposure prophylaxis in Australian men who have sex with men

The optimal implementation of doxycycline post-exposure prophylaxis (doxy-PEP) for preventing bacterial sexually transmitted infections (STIs) among Australian men who have sex with men is unclear due to concerns about antimicrobial resistance and cost-effectiveness. We developed an individual-based model, calibrated to Australian national data, to compare five targeted doxy-PEP strategies with a base case from 2025 to 2034, using a multi-criteria ranking framework to evaluate their epidemiological, resistance, and economic outcomes. All evaluated strategies reduced STIs by 13.0% to 47.8% and were cost-saving. However, compared to the high 73.5% baseline projection for high-level tetracycline resistance by 2034, all strategies yielded higher proportions. This proportion was highest (97.4%) when targeting all HIV pre-exposure prophylaxis users, and lowest (81.2%) for the syphilis diagnosis strategy. This syphilis-focused strategy reduced overall STIs by 16.4%, had the highest benefit-cost ratio (9.2), and ranked highest in 9 of 11 evaluation frameworks. Here, we show that doxy-PEP is an effective, cost-saving intervention, with the syphilis diagnosis strategy representing the most recommended approach to optimally balance benefits and risks. Doxycycline has been recommended as post-exposure prophylaxis for prevention of bacterial sexually-transmitted diseases. Here, the authors use mathematical modelling to investigate the potential disease, antimicrobial resistance, and economic implications of this intervention in gay, bisexual, and other men who have sex with men in Australia.