Project Summary Gay, bisexual and other men who have sex with men (GBMSM) remain a population in the U.S. for whom the burden of HIV is high and disproportionate, particularly among younger GBMSM and GBMSM of color, for whom HIV incidence continues to rise despite decades of HIV prevention research to curb the epidemic. However, even among these highest risk groups, risk for infection is not equivalent and the goal of this study is to better understand what factors differentiate levels of risk for HIV infection. Research to date suggests that this disproportionate burden is likely to be exacerbated by psychosocial disparities faced by this population in the form of syndemics and sexual minority stress. However, research on these factors has been limited by a focus on risk for HIV infection operationalized as risk behavior or cross-sectional prevalence of HIV, making actual vulnerability to infection and temporal associations difficult, if not impossible, to determine. We are submitting this application in response to RFA-AI-16-031 Limited Interaction Targeted Epidemiology (LITE) to Advance HIV Prevention (UG3/UH3). We propose to recruit and enroll a large and diverse cohort of approximately 8,000 GBMSM ages 16 and older in the U.S. and Puerto Rico who are at high risk for infection. We will utilize mobile sexual networking applications (“mobile apps”) to identify and enroll these men both to allow for rapid and efficient recruitment and because these apps rapidly increasing in popularity, with research demonstrating that men who use mobile apps are at higher levels of risk for HIV infection than GBMSM recruited through other means. Using this cohort, we will work to achieve three primary aims: (1) we will establish HIV prevalence as well as prevalence of rectal sexually transmitted infections (STIs; gonorrhea and chlamydia) at baseline and subsequently establish rates of HIV and rectal STI incidence among these men 12 months thereafter; (2) we will utilize baseline levels of syndemic, minority stress, and other relevant psychosocial risk factors to develop a model of those modifiable factors that contribute to increased risk for HIV seroconversion (i.e., incidence) as well as rectal STI infection; (3) we will utilize the model to target men in the highest quartile of risk for HIV seroconversion in the cohort and follow them every 6 months thereafter for an additional two years to examine the predictive utility in prospectively predicting HIV seroconversion as well as time to seroconversion. Developing a model of modifiable psychosocial risk factors for actual HIV seroconversion and subsequently testing its reliability and validity in a prospective design has high potential to improve the next generation of HIV prevention interventions aimed at reducing disparities for this population.