Project Summary In the U.S. women who use illicit drugs (WWUD) have disproportionately high rates of infectious (e.g., HIV, HCV), chronic, and pulmonary diseases that elevate their risk for COVID-19. Their health and disease profile is driven by enduring social conditions (e.g., scarcity of income, food insecurity, access to health services, housing, discrimination). These prevailing social conditions can also undermine WWUDs’ ability to protect themselves from COVID-19 (e.g., washing hands, social distancing). Drug procurement and use, which are largely social processes, further challenge these self-protection measures. Testing and future vaccination is vital to reducing COVID-19 among this high-risk population, necessitating accessible testing schemes. We propose a mixed methods study that draws upon the Andersen Behavioral Model10 and is grounded in eco-social theory. Specifically, the Baltimore-based study aims to: 1) explore predisposing social factors (e.g., housing, food security), individual-level factors (e.g., drug use, mental health), and beliefs (e.g., medical mistrust) that are facilitators and barriers of COVID-19 testing and perceived risks (e.g., income generation, violence) resulting from a diagnosis through in-depth interviews among WWUD (N=15) and a cultural domain analysis (N=45); 2) gain an understanding of the enabling community-level environment (e.g., medical and social service agencies that currently serve WWUD, existing city-wide COVID-19 testing sites) that could facilitate or hinder WWUDs’ COVID-testing uptake through observations (N=8-10) and key informant interviews (N=10); and examine predisposing social factors, individual-level factors, and beliefs that are associated with COVID-19 testing and retesting among a cohort (N=250) of WWUD at baseline and 3-month follow-up. Optional testing offered at both study visits will be a self-administered, rapid antigen test. We will also examine the role of medical mistrust in shaping women’s use of healthcare services as well as experiences of stigma and discrimination in healthcare settings, particularly among Black participants. In Baltimore, this mistrust is particularly pronounced, with Johns Hopkins Hospital having a long history of mistrust in the Black community owing to experimentation and deception of research engagement. The study will be guided by a community advisory board (CAB) who will inform its design and implementation as well as engage in disseminating the results at community meetings to inform COVID-testing scale up.