ABSTRACT – Modified for administrative supplement, underlined Outbreaks of HIV and HCV in rural areas of the Midwest have been associated with syringe-sharing among partners injecting nonmedical prescription opioids. Illinois ranks as the third highest state in percentage increase in death rates involving synthetic opiates between 2014-2015. The southernmost 16 counties of Illinois comprise the Illinois Delta Region (IDR) and share many of the characteristics of rural areas that have experienced recent HIV epidemics. A deeper understanding of community characteristics, including transitions from oral to injection opioid use, circumstances for high-risk injection practices, impact of race and the effects of structural racism, as well as heterosexism and cisgenderism including accessibility to existing and potential health-related resources will be essential to developing models of disease prevention and treatment. Partnering with state and local public health other state agencies, community-based programs, local coalitions and healthcare systems, we will take a mixed analytical approach using, predictive modeling, GIS analysis, qualitative and survey analysis, network methods, and infectious disease epidemiology to understand geospatial and sociocultural factors impacting health outcomes in people who inject drugs in the IDR. In this supplement we will develop meaningful partnerships with Black and sexual and/or gender minority (SGM) identifying communities in the study area to ensure shared goals, priorities, and processes within the context of drug use and harm reduction research and increase recruitment of Black and SGM identifying individuals into the ETHIC parent study. We will refine current instruments to ensure the optimal exploration and contextualization of potential social, cultural, and medical/structural drug use introduction and continuation pathways, drug types, routes of administration, sharing behaviors, drug use networks, and knowledge and awareness, acceptability, and utilization of harm reduction and addiction treatment with particular focus on salient factors for Black and SGM identifying communities. These data will inform evidence-based, culturally competent and inclusive interventions to strengthen access to disease screening and linkage to care and treatment, expansion of needle exchange and naloxone overdose programs, screening and referral to substance use treatment, and telehealth capacity building for the provision of PrEP, HCV management, and medication-assisted treatment for substance use disorder.