Project Summary Young men who have sex with men (YMSM) are at high risk for HIV?particularly YMSM of color. Pre-exposure prophylaxis (PrEP) is extremely effective at reducing HIV transmission. Uptake has been lower than anticipated, but is increasing rapidly?though less so among Black YMSM. PrEP effectiveness hinges upon adherence, but levels of adherence vary and tend to be lower among Black individuals and youth. Adherence to daily PrEP does not need to be perfect to obtain benefit?in the iPrEx open-label extension, taking 2-3 doses/week was 84% efficacious (4+ was 100% efficacious)?and non-daily dosing strategies are also under investigation (event- and time-driven dosing). Beyond adherence, patterns of use are critically important. Oral PrEP is unlikely to be a life-long strategy for most, and evidence suggests that many YMSM discontinue PrEP (particularly Black and Latino YMSM), but most discontinuers report continued HIV risk behaviors. Further, studies are beginning to examine episodic PrEP use during discrete periods of highest HIV risk. Finally, risk compensation (i.e., decreased condom use after initiating PrEP) is a crucial component of PrEP effectiveness as it may maintain, or even increase, HIV transmission if adherence is not optimal. The goal of the current proposal is to characterize PrEP adherence across dosing strategies, describe patterns of use (continuous, episodic, discontinuation), and examine racial differences in adherence and patterns of use. We will embed novel mixed-methods research into RADAR, a diverse cohort of YMSM (N>1,200; age 16-29) assessed every 6 months (U01DA036939). We propose to add a daily diary study of PrEP users to characterize adherence and patterns of use, biomarkers of adherence to objectively measure PrEP coverage, and in-depth interviews with PrEP users to understand contextual influences on these issues. Aim 1: Describe PrEP adherence, dosing strategies, and usage patterns among YMSM. We will conduct a 3-month daily diary study with 120 YMSM PrEP users from RADAR to: a) characterize patterns of PrEP dosing strategies (daily, time-driven, event- driven), adherence, and usage patterns (continuous, episodic, discontinuation); b) Examine whether PrEP adherence or dosing strategies are associated with self-reported sexual risk behavior and STI infection; and c) describe racial differences in PrEP adherence, dosing strategies, and risk compensation. Aim 2: Assess associations between usage patterns and long- and short-term concentrations of PrEP in red blood cells. We will collect dried blood spot samples once per month during the diary study (3x) to assess concentrations of tenofovir-diphosphate and embtricitabine-triphosphate. Aim 3: Characterize YMSM perspectives on adherence, usage patterns, and risk compensation. We will conduct in-depth interviews with 60 YMSM diary study participants to understand individual, interpersonal, and structural influences on PrEP adherence and patterns of use, with an emphasis on understanding racial differences. Data from this study will inform the development of public health messaging and behavioral interventions to improve PrEP effectiveness among diverse YMSM.