ABSTRACT Despite advances in HIV diagnostics, care and prevention strategies, infection rates among adolescent and young adult sexual and gender minorities (SGM) continue to rise in the United States (US). There is an urgent need to describe the epidemiology and trajectories of HIV acquisition in this population and to offer age and culturally appropriate scalable prevention interventions to those at highest risk of infection in the US. This project will engage and retain young SGM in an innovative longitudinal cohort, enroll them in a dynamic established digital health retention platform (HMP; HealthMPowerment), monitor HIV risk and prevention behaviors and explore the socioecological factors that influence the use of new HIV prevention technologies (UG3 phase), while also allowing targeted testing of novel digital health interventions (UH3 phase). We will also test the efficacy of expanding the core version of HMP (HMP Basic) by adding adherence tools (HMP Enhanced) for those who are on PrEP or ART to improve adherence and persistence. In Aim 1, we will enroll and retain a large (n=6000; 3000/year), diverse cohort of sexually active, SGM adolescents and young adults, ages 13-34, using innovative digital recruitment, engagement and retention strategies. Over the course of the study, we will longitudinally characterize the sexual behavior, HIV transmission risk, and PrEP uptake trajectories of SGM youth utilizing epidemiological trajectory analyses to identify the most effective points of intervention (Aim 2). For Aim 3, we will launch a randomized clinical trial to examine the efficacy of HMP Enhanced to improve PrEP adherence among HIV-negative youth (n ≥750) and ART adherence among HIV-positive youth (n ≥150) compared to HMP Basic. Finally, we will maximize the productivity of the cohort by testing new and innovative digital health devices, HIV/STI diagnostics and interventions, informed by the previous aims as well as emerging NIH prevention priorities (Aim 4). Our investigative team has decades of experience with recruitment, prevention and care of SGM youth and large-scale longitudinal cohort studies. This study will capitalize upon productive existing partnerships and digital health expertise to articulate the drivers of the ongoing HIV epidemic among the most vulnerable populations in the US in order to identify the most effective, expeditious and scalable strategies to address this ongoing public health crisis.

PROJECT NARRATIVE The proposed research project has high relevance to public health because it focuses on sexual and gender minority (SGM) youth, particularly Black and Latinx, gay, bisexual and other men who have sex with men (GBMSM) and transgender and gender diverse populations that have been devastated by the HIV epidemic in the United States. This study supports the National HIV/AIDS Strategy’s focus on HIV treatment and prevention for the most impacted US populations. The development of a large, digital community of SGM youth also aligns with the NIH’s focus on reducing stigma and addressing co-morbidities and barriers to adherence and retention in HIV care and preventative services.