Doxy4STICare - Doxycycline for Sexually Transmitted Infections; A Comprehensive Assessment of Antimicrobial Resistance and Engagement - 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 (MSM), 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) Create a prospective cohort of 500 participants (300 Doxy-PEP users, 200 eligible non-users as a comparator group) 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 prospective 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 100 sexual partners of the cohort 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.