Abstract Despite the availability of effective HIV prevention tools such as pre-exposure prophylaxis (PrEP), significant disparities persist among communities of color, particularly among women in the Deep South where the rate of HIV infection is fourteen-times higher for Black women compared to White women. PrEP utilization remains low among women in the Deep South with estimates of <7% eligible women receiving PrEP in Alabama. Moreover, algorithms to determine PrEP eligibility demonstrate poor predictive power for women. The proposal takes advantage of a dynamic and innovative collaboration of experienced HIV-prevention investigators from the University of Alabama-Birmingham, University of North Carolina-Chapel Hill, Centers for AIDS Research, the Alabama Department of Public Health (ADPH), and Social Scientific Systems. This novel research proposal utilizes a population-based approach to establish a geographically representative cohort of cis- and trans-gender women (‘Camellia Cohort’) at significant risk for future HIV acquisition, based on recent gonorrhea or syphilis infection, across the state of Alabama (AL), highlighted as a geographic hotspot by the federal Ending the HIV Epidemic strategy, to better understand factors associated with risk of STI and HIV diagnosis and predictors for PrEP use. The aims of this proposal are to: 1) refine the HealthMpowerment (HMP) digital platform, previously utilized to deliver evidence-based interventions to improve HIV and prevention outcomes among Black men who have sex with men and transgender women, to include key elements that optimally engage and retain a cohort of women at-risk for HIV in AL; this will be achieved via stakeholder engaged research with self-identified women on PrEP and PrEP care team members using nominal group techniques; 2) recruit and retain a geographically-diverse and rurally-enhanced cohort of 800 women ages 18-44, with recent positive gonorrhea or syphilis testing who are STI- and HIV-uninfected at enrollment, to participate in the Camellia digital cohort utilizing a geographically diverse sampling framework using public and commercially available annual county-level HIV and STI testing data and 3) evaluate predictors, mediators and moderators for STI/HIV incidence and PrEP use and adherence in the Camellia Cohort by collecting demographic, behavioral, and community level assessments via the HMP digital platform and HIV/STI testing through ADPH’s home testing program at regular intervals; we will purposefully sample women with high HIV vulnerability and/or PrEP use within the cohort for in-depth interviews (n = 30) to further explore factors contributing to PrEP use to guide future intervention development. This research will lay the groundwork for a larger research program testing the implementation of a further adapted HMP digital platform designed to improve HIV/STI testing, PrEP utilization and persistence among women in the Deep South, focusing on areas with higher HIV...