PROJECT SUMMARY There is a critical need to better understand the epidemiology of HIV acquisition in the United States (US), particularly among cisgender gay, bisexual and other men who have sex with men (MSM), one of the key populations essential to target for End the HIV Epidemic (EHE) initiatives. In direct response to RFA-AI-21-018, this study will use innovative technology to recruit and retain a large cohort of high-risk, HIV-negative young men who have sex with men (YMSM) focusing on racial/ethnic minority YMSM and high HIV prevalence geographic areas (known as “hot spots”). Furthermore, we will leverage this cohort to conduct a large-scale clinical trial while maintaining the standard of care control arm as a longitudinal observational cohort for epidemiologic analyses. Our study team is uniquely positioned and has all the relevant expertise to conduct this study having successfully recruited and retained more than 12,000 YMSM in a full range of research studies across the HIV continuum (e.g., epidemiology, intervention development, mHealth, PrEP, clinical trials, innovative geospatial methods). We have had specific success conducting prevention research with YMSM (17-25 years), including racially and ethnically diverse YMSM, our target demographic group. Further, we have previously leveraged advanced social media advertising techniques and used innovative geospatial analytics to target/study “communities within communities”, reaching hard-to-reach YMSM from diverse geographic areas (e.g., rural zip codes, U.S. tribal lands, etc.) and young ages (e.g., YMSM 13-18 years of age). We will harness innovative technology to recruit, during 36-months of enrollment, and then retain a large cohort (N = 5,000) of 17-25 year old YMSM, the majority being Black and Latino, who are at high-risk of HIV transmission (e.g., history of condomless anal sex) and follow them every 6 months thereafter. We will conduct an entirely virtual, digital clinical trial (Specific Aim #1) testing whether MyPEEPS Mobile (an evidence-based mHealth HIV prevention intervention) reduces HIV incidence among HIV-negative YMSM (17-25 years old) looking at the influence of theory-driven social, ecological, and geospatial factors on intervention uptake and efficacy inclusive of measures that align with traditional models of behavior change such as the Information Motivation Behavior Model. A social-ecological theoretical framework will also guide the analysis of the longitudinal observational cohort study (Specific Aim #2) of the 2,500 control arm participants to assess individual, network, geospatial, and public policy correlates of HIV risk and health seeking behaviors (e.g., PrEP uptake) comparing individuals who become HIV-positive to those who do not. Intervention Implications. The findings from this research will have important real-world implications for research and practice. For example, understanding how individual, network, geospatial, and public policy factors correlate with HIV incidence and moderate intervention effects will help inform how and where interventions should be delivered.

PROJECT NARRATIVE Addressing the End the HIV Epidemic initiatives, this study will use innovative electronic methods (e.g., social media with community informed advertisements) to recruit and retain a large (N=5,000), diverse national sample of high-risk young men who have sex with men (YMSM) 17-25 years of age to better understand correlates of HIV-related sexual risk and HIV incidence within the context of a theoretically-grounded social- ecological framework. In addition to the epidemiologic aim of the proposed research, we will test the efficacy of MyPEEPS Mobile, a promising mHealth HIV prevention intervention in reducing HIV incidence among YMSM.