Multilevel strategies to understand and modify the role of structural and environmental context on HIV inequities for sexual and gender minorities of color - PROJECT SUMMARY/ABSTRACT Black, Latino/a/e/x, and Multiracial (BLM) sexual and gender minorities who have sex with men (SGMSM) in the U.S. continue to experience a high and disproportionate burden of HIV, particularly younger BLM SGMSM for whom HIV incidence continues to rise despite advances in HIV prevention. Evidence suggests that differences in individual risk behaviors do not account for HIV inequities, and underscore the need to move beyond models of individual-level risk factors to identify and intervene upon the socio-structural factors that create and maintain inequitable risk environments. However, much of the research to date is limited in scope and focuses individual-level risk or on cross-sectional HIV prevalence, which limits the ability to treat socio- structural factors as dynamic or to investigate the environments within which risk behaviors occur. We are submitting this application in response to RFA-AI-21-018 Limited Interaction Targeted Epidemiology to Advance HIV Prevention (UG3/UH3). We propose to enroll a cohort of approximately 5,500 BLM SGMSM ages 16 and older in the U.S. and Puerto Rico who are at high risk for HIV infection. We will use a combined approach to recruitment (sexual networking apps, social media, and other digital recruitment techniques) that is adaptive to known shifts in digital technology. Participants will complete a survey and home-based sampling for lab-based HIV testing at enrollment and annually thereafter for three years and an ecological momentary assessment (EMA) for six weeks after enrollment. Concordant with study enrollment, we will develop novel metrics to quantify socio-structural factors (state-level policy and social climate indicators) that create intersectional oppression for BLM SGMSM, specifically structural racism, anti-LGBTQ stigma, and restrictive HIV-related healthcare (Aim 1a). We will subsequently utilize the newly developed metrics from Aim 1a along with local socio-structural factors (local-level HIV prevalence and socioeconomic indicators) and baseline and EMA data to test the inequitable risk environments hypothesis to understand the role of state and local socio- structural risk factors in HIV risk—this hypothesis will specifically test both the impact of socio-structural factors on daily exposure to intersectional stigma and the interaction of socio-structural risk with individual behaviors on undiagnosed HIV infection at baseline (Aim 2). These data will also be used to test a longitudinal model of mechanisms through which state and local socio-structural factors directly and indirectly influence HIV seroconversion and access to emerging HIV prevention technologies (e.g., emerging PrEP modalities) (Aim 3). Study findings will be systematically reviewed and translated into guidelines for Ending the HIV Epidemic- related public health policy and community-level interventions to reduce HIV inequities (Aim 1b). Developing and testing a socio-structural model of HIV risk has strong potential to move the field beyond individually- focused models of risk and improve the next generation of HIV prevention interventions aimed at reducing disparities for this population.