Project Abstract In collaboration with the Shelby County Health Department, which has jurisdiction over Memphis as well as rural northwest Mississippi and Arkansas, we propose to inform policy decisions towards improving HIV outcomes for population-level and subgroup-specific HIV goals in three diverse settings that together typify high incidence locations in the U.S. HIV epidemic (New York City, Memphis, and northwest Mississippi). We will use mathematical modeling to simulate alternative ways to distribute resources across interventions, settings, and target populations to reduce HIV incidence and improve overall health. Our analyses will be distinguished by incorporating screening and responding to CASM conditions (Conditions of Alcohol, Substance and Mood), measures of inequality-aversion (i.e., willingness to trade-off some aggregate benefit in order to distribute it more equally) towards vulnerable subgroups, and the promising new modalities of long- acting-injectable PrEP and ART. Our partners at the Shelby County Health Department and their larger group of stakeholders will provide context on local HIV infection patterns and feasibility and acceptability constraints to inform modeling analyses.