ABSTRACT The HIV epidemic continues to disproportionately affect individuals with health disparities. Marginalization, substance use disorder, stigma and other health disparities contribute to decreased mood which influences key health behaviors like adherence to oral HIV pre-exposure chemoprophylaxis (PrEP). These key disparities contributed to the world failing to achieve the UNAIDS 90-90-90 goals in 2020 to end the HIV epidemic. One of the pillars to ending the epidemic is improving uptake and persistent to PrEP. While efficacious, men who have sex with men (MSM) with substance use disorders (SUD) experience multiple intersectional marginalized identities which lead to PrEP nonadherence. Technologies to detect PrEP adherence patterns continue to be developed to advance interventions that support adherence. The parent award, K23DA044874, develops a preventive intervention, PrEPSteps, that leverages an ingestible radiofrequency transmitter (digital pill system) to directly measure adherence. This digital pill then drives personalized adherence skills training that addresses PrEP nonadherence at the moment it occurs. In this administrative supplement, we will integrate measures of health disparities including the intersectional discrimination index and profile of mood states into the fabric of the parent pilot randomized controlled trial to understand mechanisms of how these health disparities influence uptake of the digital pill intervention and PrEP adherence. We will additionally conduct formative qualitative interviews among parent study participants and healthcare providers who prescribed PrEP grounded in the Consolidated Framework for Implementation Research (CFIR) to understand how health systems may implement digital pills to measure PrEP adherence with a lens of health disparities.