Project Summary RFA-AI-16-031 (LITE) is designed to address critical needs in HIV prevention research by using innovative technology to enroll and follow large-scale epidemiological cohorts of those at highest risk of infection. The proposed project will utilize established Internet-based strategies, previously used successfully by the research team, to enroll a sample of 5,000 high-risk HIV-negative gay, bisexual, and other men who have sex with men (GBM) ages 16 to 49—the population representing the highest percentage of new infections annually—and follow them prospectively for four years. The design features of our proposal were chosen specifically to: (a) identify individual-, network-, and contextual-level predictors and correlates of HIV seroconversion, (b) identify missed HIV prevention opportunities among those seroconverting during the course of the study, and, thus (c) inform interventions to further reduce acquisition and transmission. We define “high-risk” as meeting CDC guidelines for PrEP treatment, but not taking PrEP. Participants will complete annual self-administered at-home rapid HIV testing (results submitted via digital photo of the test paddle) as well as brief (~20 min) at-home computerized surveys. In addition to being referred for treatment, study participants who seroconvert will complete a semi-structured telephone interview to identify missed HIV prevention opportunities and the contextual factors involved. We will monitor newly diagnosed participants' movement through the HIV care continuum. Based on current incidence rates, we anticipate accumulating ~252 infections during the study; however, because we are targeting high-risk men, this number could be higher. Aim 1 (UG3 Phase): Establish a cohort of 5,000 high-risk HIV-negative GBM who are not on PrEP, all of whom complete baseline online surveys and at-home self-administered HIV testing, as well as consent for longitudinal follow-up. Determine PrEP uptake and HIV incidence 12 months after study enrollment. Supplemental Aims: Using the cross sectional data from GBM deemed ineligible during screening for study eligibility: Sup. Aim 1a—Estimate the uptake of PrEP; and Sup. Aim 1b—Characterize missed HIV prevention opportunities (e.g., reasons for no prior PrEP use) among recent HIV seroconverters. Aim 2 (UH3 Phase): Follow the cohort for four years to characterize (2a) individual/network/contextual-level determinants of PrEP uptake/discontinuation; (2b) new HIV seroconversions and missed HIV prevention opportunities, including individual/network/contextual-level determinants; (2c) racial/ethnic disparities in HIV incidence and their trends over time; and (2d) the influence of PrEP uptake on racial/ethnic disparities.