Sexually transmitted infections (STIs) represent a significant public health challenge, with increasing
prevalence worldwide. Disproportionately affecting young individuals, gay and bisexual men who have sex with
men (gbMSM), persons with HIV or on HIV prevention medications, and racial and ethnic minorities, effective
prevention strategies are essential. Doxycycline post-exposure prophylaxis (Doxy-PEP) has been shown to
reduce bacterial STIs; however, knowledge gaps remain, and there are concerns about engagement, effective
use, and the potential antimicrobial resistance consequences. This study proposes a threefold approach to
address these questions. (1) Establish a prospective cohort of 300 Doxy-PEP users (Doxy-PEP cohort) to
examine baseline and longitudinal factors mapped to the information-motivation-behavioral skills theoretical
framework and identify factors associated with Doxy-PEP care engagement and effective use. (2) Collect
biological samples from the Doxy-PEP cohort and enroll 100 Doxy-PEP eligible non-users (Control cohort) to
evaluate the impact of antimicrobial resistance in persons taking Doxy-PEP using laboratory methods including
culture and resistance testing and metagenomics. (3) Collect biological samples from up to 600 sexual
partners of the Doxy-PEP and control-cohorts to assess the potential for transmission of bacteria between
sexual partners using comparative genomics. By addressing these aims, the study will provide valuable
insights into the risks, benefits, implementation, and impact of Doxy-PEP, informing future strategies to
optimize engagement and maximize STI incidence reduction while minimizing antimicrobial resistance risks.
