PROJECT SUMMARY Young African American (AA) and Hispanic/Latino (H/L) MSM bear a disproportionate share of the HIV disease burden in the United States (US). Pre-exposure prophylaxis (PrEP) is highly effective in reducing HIV acquisition risks among MSM, but its ability to reduce HIV acquisition among AA and H/L MSM hinges on optimal implementation and expanded use in “real-world” clinical settings. Preliminary studies demonstrate that AA and H/L initiate PrEP and are retained in PrEP care at lower rates than their White counterparts, but little is known about longer-term adherence and retention in PrEP care among AA and H/L MSM. The manner in which structural, social, and individual level factors impact PrEP outcomes in real-world settings, particularly among young AA and H/L MSM, are not yet well understood. MSM who initiate PrEP may change behaviors (e.g., enter a monogamous relationship with an HIV negative partner) and no longer be indicated for PrEP. Furthermore, it is largely unknown why individuals, especially AA and H/L MSM, are not retained in PrEP care which complicates development of appropriate interventions to enhance retention in PrEP care. This proposed study follows a longitudinal, observational cohort (n=450) of White, AA and H/L MSM in real-world PrEP programs in Mississippi, Missouri, and Rhode Island to both characterize a PrEP care continuum and predict why MSM are sub-optimally adherent or lost to care, with a focus on measuring racial and ethnic disparities (Specific Aim 1). We will conduct individual interviews with MSM who are prescribed PrEP but sub-optimally adherent or drop out of PrEP care (Specific Aim 2) to elucidate reasons for sub-optimal adherence and retention and to identify components of potential interventions to improve adherence and retention in care. Using data from our longitudinal cohort, we will perform microsimulations in the context of an agent-based model to evaluate the impact of sub-optimal PrEP adherence and retention in care on HIV incidence in three diverse US settings. We will then predict the impact of potential interventions on PrEP care continuum outcomes (Specific Aim 3).