Project Summary Since 2012, pre-exposure prophylaxis (PrEP), typically delivered as a daily pill or more recently as a bimonthly injection, has been available as a method of HIV prevention. Despite PrEP being highly effective at reducing a person’s risk of acquiring HIV, uptake of the prevention method has been low – especially in the Southern US, which is already disproportionately impacted by HIV. In this study we will examine existing programs implementing PrEP and assess which implementation strategies and contextual factors lead to the best rates of PrEP initiation and persistence; these findings will contribute to improving PrEP delivery and the ongoing Ending the HIV Epidemic efforts in the south. The study contains two aims: Aim 1) Identify the implementation strategies and contextual factors affecting PrEP implementation within clinical and community-based organizations in southern EHE counties and Aim 2) Determine the combination(s) of implementation strategies and contextual factors that produce the most effective delivery of PrEP to populations at greatest risk of HIV acquisition. To achieve Aim 1 we will collect and summarize data through three phases. In Phase 1 we will request aggregate data from organizations that conduct HIV prevention and PrEP-related activities in Hillsborough, Pinellas, Tarrant, and Dallas Counties to measure the study outcomes (i.e., the proportions of eligible individuals who start PrEP and who have maintained PrEP use over 3-month and 6-month periods) and identify preliminary variation in the implementation strategies and site-level contextual factors that may affect PrEP implementation. In Phase 2 we will conduct quantitative surveys with staff members at a subset of sites to assess the impact of CFIR factors and presence or absence of implementation strategies on PrEP implementation outcomes. In Phase 3 we will complete semi-structured interviews to gain a more detailed and nuanced understanding of implementation strategies, contextual factors and within-site variation from Phase 2 responses. To achieve Aim 2 we will conduct Coincidence Analysis (CNA) to determine the sets of implementation strategies and contextual factors leading to high proportions of eligible individuals who both start and maintain PrEP (i.e., optimized implementation). CNA is a method of causal inference and determines the combinations of factors that are minimally necessary or sufficient for an outcome of interest. In this application we will examine which combinations of contextual factors and implementation strategies result in optimized PrEP implementation. The models will be run for three outcomes based on the following: proportion of clients who initiate PrEP; and proportion of clients continuing PrEP use after 3 and 6 months, each of which will either be dichotomized (high vs. low) or trichotomized (high, medium, low). Additional factors, representing differences in client populations (e.g., MSM, women, youth) will be included...