Identifying Community-Informed DoxyPEP Implementation Strategies to Guide Equitable Delivery of Syphilis Prevention - Project Summary/Abstract In this R21 proposal, we will use implementation science approaches to study delivery of equitable syphilis prevention, doxycycline post-exposure prophylaxis (doxyPEP), in a clinic-based setting. Innovative strategies for syphilis prevention are needed to address the growing national epidemic, with disproportionate burden of disease among Black and Hispanic/Latinx sexual and gender minority persons (SGM) who have sex with men. In Chicago specifically, syphilis rates have been rising steadily, syndemic with HIV transmission. Existing public health responses – contact tracing, testing, and treatment – have not stemmed these rising rates. Recent data show that doxycycline, taken after sexual activity, is very effective at prevention of syphilis for those who may be exposed. As an emerging evidence-based intervention, key implementation information is needed to ensure equitable delivery of doxyPEP to maximize impact on the syphilis epidemic. As has been recognized with other biomedical prevention tools such as HIV pre-exposure prophylaxis, early identification of barriers to delivery is imperative. The proposed study will address gaps in doxyPEP delivery using implementation frameworks in partnership with an SGM-focused health system in Chicago, Illinois, to meet the following aims: 1) Assess determinants of doxyPEP use at the patient, provider and health system levels; 2) Identify and select community- informed implementation strategies to support doxyPEP use among populations most affected by the syphilis epidemic; and 3) Develop and evaluate acceptability, feasibility, and appropriateness of a doxyPEP implementation strategy package among patients, providers, and health systems stakeholders. Our mixed methods approach will be rooted in the Consolidated Framework for Implementation Research (CFIR) and the Capability, Opportunity, and Motivation Model of Behavior (COM-B), incorporating qualitative methods and conjoint analysis approaches, to identify important determinants of doxyPEP service delivery. The proposed research will result in implementation strategies to guide equitable use of doxycycline post-exposure prophylaxis among populations most impacted by syphilis.