PROJECT SUMMARY Despite the availability of biomedical prevention tools to end the HIV epidemic, incidence of HIV and other STIs in Alabama remain high, while uptake of prevention such as PrEP remains low. Further, opioid prescribing, use, and overdose-related death are also disproportionately high in Alabama, with an increasing impact on Black individuals. Converging risk related to HIV, STIs, and drug use can be attributed in part to socioeconomic inequalities in the Deep South which may drive sex work. Recent evidence suggests individuals engaged in sex work report higher rates of diverse drug use and increased vulnerability to HIV and other STIs compared to other individuals in Alabama. Sex workers and people who use drugs represent vulnerable groups who face unique barriers to HIV prevention including PrEP. However, HIV services for sex workers in Alabama are limited, and no evidence-based interventions in the CDC’s Compendium have been tailored for sex workers. Through community-academic partnership, this project will use syndemic theory to directly address the needs of a severely underserved population through development of a PrEP intervention for people engaging in sex work in Alabama. The Specific Aims are to: (1) Develop a harm reduction intervention that responds to syndemic drug use, HIV, and STIs for people engaged in sex work, [Year 1] and (2) Pilot and evaluate the acceptability, appropriateness, and feasibility of the intervention to increase PrEP uptake among people engaged in sex work [Year 2]. Within Aim 1, we will leverage existing quantitative data to identify intervenable Outer Setting characteristics (patient needs and resources) and collect de novo qualitative data to further characterize sex work, contextualize the needs and resources of individuals engaged in sex work, and characterize the processes and resources of Birmingham AIDS Outreach (BAO) to inform intervention approaches. Under Aim 2, pending CFAR renewal, we will pilot the intervention at BAO with 40 individuals engaging in sex work, and will evaluate the intervention’s acceptability, appropriateness, and feasibility from a participant and provider perspective. We will assess clinical outcomes and preliminary effects on PrEP use and uptake of harm reduction strategies (use of condoms and sterile syringes). This work will be guided by the Consolidated Framework for Implementation Research (CFIR), RE-AIM framework, and ERIC strategies. The project will result in formation of a Health Equity Research Assembly, development of a novel harm reduction intervention for people engaged in sex work, and, if Year 2 is awarded, pilot data to inform a subsequent R- level proposal.