ABSTRACT Different facets of stigma (anticipated, enacted, internalized) associated with substance use disorder (SUD) and with HIV positive status impede cessation of substance use and HIV health outcomes including antiretroviral therapy adherence and viral load suppression.1-6 Although public stigma is pervasive surrounding both, individuals can learn to reduce its internalization and mitigate stigma’s negative impacts on their health. However, interventions promoting this are non-existent in the published literature. To this end, we propose to adapt an evidence-based stigma-impact reduction intervention, Ending Self- Stigma (ESS) to reduce stigma and its negative impacts on health. ESS has shown efficacy in reducing internalized and anticipated stigma in populations experiencing mental health conditions.7 The 9-session group-based intervention, which uses cognitive behavioral therapy strategies and social cognitive theory constructs, employs didactic learning and interactive activities to facilitate reductions in internalized and anticipated stigma. The purpose of the proposed study is to adapt the ESS intervention for people living with HIV (PLWH) who also have opioid use disorder (OUD) and/or cocaine use disorder (CUD). In the first year, we will use an iterative process that starts with formative interviews with service delivery key informants and people living with PLWH with OUD and/or CUD, and ends with two successive pilot studies with the study population. Through this process, intervention content will be adapted for this population and intervention delivery will be adapted for a virtual format via a web-based platform. Then, in years 2-3, a small randomized clinical trial of the resulting Ending Self-Stigma intervention adapted for PLWH with Substance Use disorder (ESS-HSU) will be conducted with 70 participants to determine its feasibility and acceptability in addition to collecting data on proximal outcomes including internalized and anticipated stigma, depressive symptoms, anxiety and perceived stress associated with stigma. We will also measure distal outcomes including ART adherence, viral load and substance use (SU) at 6-month follow-up. The ESS-HSU intervention has the potential for high public health impact by reducing the negative effects of internalized and anticipated stigma resulting from the pervasive public stigmatization of HIV seropositive status and SUD on HIV health outcomes and cessation of SU. ESS-HSU would be the first virtual intervention of this type to be evaluated in a randomized clinical trial. If results are promising, we will seek R01 funding for a full-scale test of this innovative intervention to determine its effects on a range of health outcomes and characterize mechanisms of intervention effects.