Potential Impact of Doxycycline Post-exposure Prophylaxis Prescribing Strategies on Incidence of Bacterial Sexually Transmitted Infections

Background Doxycycline post-exposure prophylaxis (doxyPEP) reduces bacterial sexually transmitted infection (STI) incidence in people with HIV (PWH) or using HIV pre-exposure prophylaxis (PrEP). Given concerns about widespread antibiotic use, we identified doxyPEP prescribing strategies to minimize use while maximizing impact on STIs.Methods We used electronic health records of gay and bisexual men (GBM), transgender women, and nonbinary people assigned male sex at birth with & GE;2 STI tests (chlamydia, gonorrhea, syphilis) at an LGBTQ-focused health center during 2015-2020. We defined 10 hypothetical doxyPEP prescribing strategies based on PrEP use, HIV status, or STI history. We estimated doxyPEP use and STI diagnoses averted in counterfactual scenarios in which people meeting prescribing criteria received doxyPEP, assuming STI rates during use would have been reduced by clinical trial efficacy estimates.Results Among 10 546 individuals (94% GBM), rate of any STI was 35.9/100 person-years. Prescribing doxyPEP to all individuals would have averted 71% of STI diagnoses (number needed to treat for one year to avert one STI diagnosis [NNT] = 3.9); prescribing to PrEP users/PWH (52%/12% of individuals) would have averted 60% of STI diagnoses (NNT = 2.9). Prescribing doxyPEP for 12 months after STI diagnosis would have reduced the proportion using doxyPEP to 38% and averted 39% of STI diagnoses (NNT = 2.4). Prescribing after concurrent or repeated STIs maximized efficiency (lowest NNTs) but prevented fewer STIs.Conclusions Prescribing doxyPEP to individuals with STIs, particularly concurrent or repeated STIs, could avert a substantial proportion of all STI diagnoses. The most efficient prescribing strategies are based on STI history rather than HIV status or PrEP use. Using electronic health records, we assessed hypothetical doxycycline post-exposure prophylaxis prescribing strategies. Doxycycline could avert a substantial proportion of sexually transmitted infection (STI) diagnoses, with the most efficient strategies based on STI history, not HIV status or pre-exposure prophylaxis use.