ABSTRACT Preventing HIV transmission with enhanced Pre-exposure Prophylaxis (PrEP) access, particularly among marginalized populations with disproportionate HIV incidence (e.g., minoritized racial/ethnic and sexual orientation and gender groups), is a crucial step in ending the HIV epidemic. Though unhealthy alcohol use is a central modifiable risk factor for HIV incidence and over-represented among marginalized populations, few HIV prevention interventions exist that synergistically address both unhealthy alcohol use and PrEP. Research is needed to understand PrEP uptake among individuals with unhealthy alcohol use and to develop scalable patient-centered interventions that synergistically address unhealthy alcohol use and HIV. The Veterans Health administration (VA) is a leader in provision of evidence-based care for unhealthy alcohol use, yet substantial gaps in PrEP implementation for Veterans with unhealthy alcohol use exist—our preliminary research suggests major gaps in PrEP knowledge, use, and reach, and Veterans with unhealthy alcohol use. Evidence-based interventions/treatments are available for unhealthy alcohol use, but alcohol use is historically under targeted in HIV prevention interventions. Our team of interdisciplinary experts in HIV and addiction medicine, the intersection of alcohol use and HIV, implementation science, health disparities research, and community-partnered research will use sequential mixed methods guided by socioecological theory, the Consolidated Framework for Implementation Science, and the Discover/Design/Build/Test (DDBT) process to understand the impact of unhealthy alcohol use on the PrEP care continuum and then refine an existing decision aid to increase PrEP initiation in primary care at the point of alcohol-related care in the VA. Quantitative work will include ~1.9 million individuals, including adequate numbers of minoritized patients (e.g., ~115,000 individuals with minoritized sexual orientation and ~11,000 individuals with minoritized gender identity) and will assess variation in patterns of PrEP initiation and persistence across VA facilities and patient subgroups (Aim 1). Findings will be used to inform purposive sampling for qualitative work to refine (Aim 2) and then pilot test an existing decision aid for developed previously with NIAAA support (Aim 3). Our study is patient-centered and innovative in characterizing PrEP care overall and within diverse subgroups of patients with and without unhealthy alcohol use, leveraging a novel natural language processing (NLP)--driven algorithm for identifying sexual minority groups, and tailoring an existing decision aid to facilitate shared decision-making for co-occurring HIV prevention and alcohol use. Study activities will be conducted with iterative input from a community advisory board. The study is highly responsive to NIAAA priorities and has potential for high impact as it will lay foundation for integrating a patient- centered and multi-targeted...