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.