SUMMARY Ending the HIV Epidemic will require multi-sectoral efforts to maximize the dissemination and availability of HIV testing and pre-exposure prophylaxis (PrEP). Pharmacies can fill an important gap in delivering PrEP to populations affected by HIV and have many advantages over conventional clinic-based care models, including increased accessibility, established community trust, and experience providing medication counseling. The overarching goal of this supplement application is to advance the science of implementing pharmacy-based rapid HIV testing and PrEP, two evidence-based practices that remain underutilized among populations affected by the HIV epidemic. This study will examine key questions regarding the implementation of pharmacy-based rapid HIV testing and PrEP initiation in communities with high burden of HIV in Philadelphia, PA, an urban area prioritized by the Ending of HIV Epidemic initiative. We hypothesize that a pharmacy-based PrEP delivery model will be acceptable, feasible, and appropriate and that individuals will uptake pharmacy- based PrEP. The study will pursue three research aims: Aim 1: Identify implementation barriers and facilitators of pharmacy-based HIV testing and PrEP initiation. Informed by the Consolidated Framework for Implementation Research (CFIR) and the Health Equity Implementation Framework (HEIF), we will conduct a mixed methods study using in-depth interviews with stakeholders and a survey of pharmacists to identify implementation determinants and assess implementation readiness of pharmacy-based PrEP. Aim 2: Determine optimal implementation strategies for pharmacy-based HIV testing and PrEP delivery. We will conduct focus group discussions with pharmacists and stakeholders to determine optimal strategies and mechanisms to maximize implementation success of the intervention. Aim 3: Evaluate the implementation of a community-based, pharmacist-led HIV testing and rapid PrEP initiation intervention. Using the Proctor framework of implementation outcomes, we will pilot the intervention in community pharmacies and conduct a mixed methods study to assess acceptability, feasibility, appropriateness, and reach of the program. The research will be implemented through a collaborative effort with partners from the Penn Center for AIDS Research, Philadelphia Department of Public Health, Philadelphia College of Pharmacy, and local community pharmacies. Completion of research aims will provide key data on an adaptable model for widespread implementation of pharmacy-based HIV testing and PrEP. Moreover, the project will support local EHE efforts by capacitating pharmacists to provide rapid HIV testing and promptly initiate PrEP. Evidence and insights generated from this research will be used to test the efficacy of the intervention at scale in a Type II hybrid effectiveness-implementation clinical trial.