Abstract Latino men who have sex with men (MSM) comprise a community that faces elevated risk for disparately negative personal and public health outcomes, including substance use, HIV, and COVID-19 syndemics, and a commuity that remains severely underserved. We propose to examine, in-depth using qualitative interviews, the psychological factors and social spaces that may contribute to substance use and higher rates of HIV among Latinx MSM. This work will supplement our parent grant, which aims to identify and prioritize geographic HIV risk and substance use hotspots among urban, Latinx and Black men who have sex with men. Our work directly engages with issues of health equity among racial and sexual minority men, and is significant because a) targeting risk hotspots is a key priority in the “Ending the HIV Epidemic” initiative, and b) personalized public health, often occurring in different venues other than traditional health facilities within the community, is an effective way to deliver appropriate HIV prevention, care, and treatment. In this supplemental proposal, we address a potential limitation to effective differentiated service delivery, such as peer-driven harm-reduction interventions, in our HIV risk hotspots specifically among Latinx MSM; namely, would these interventions work with socially-isolated individuals who engage in substance use? To achieve our goals, we will sample 40 Latino MSM aged 18-40 who previously participated in our Activity Space research, a study that leverages the NIDA-funded mSTUDY. Our specific aims are: 1) To identify and understand how psychological health factors during COVID-19 (e.g., loneliness, psychological distress) and social network factors (e.g., social isolation, sparse social networks) activate or amplify substance use in HIV risk hotspots; and 2) To assess the acceptability and feasibility of differentiated risk- reduction interventions among Latinx MSM who use substances in the context of the COVID-19 pandemic. The goal-oriented outcome of this work will be additional knowledge on how to best prioritize risk-reduction interventions in Latinx communities outside of healthcare settings. Data will inform the development of community-based prevention and clinical interventions that incorporate key psychological issues, including unique challenges associated with the COVID-19 pandemic, and will therefore have a stronger impact among Latino MSM.