Sexually transmitted infections (STIs) represent a significant public health challenge, with increasing rates worldwide.  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 Doxy-PEP users 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 Doxy-PEP eligible non-users 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 sexual partners of participants 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.