PROJECT SUMMARY The number of acute hepatitis C virus (HCV) infections has risen steadily in the U.S. due to increased injection drug use (IDU). The growth of IDU has disproportionately contributed to acute HCV infections in rural communities as their incidence rates are more than twice those of urban areas. HCV management is described using the HCV cascade of care (CoC) and includes testing and treatment completion. There is a critical need to increase HCV testing among people who inject drugs (PWID). The annual HCV testing rate is only 7.7% among those clinically identified as PWID in the U.S. Among rural PWID who tested positive for HCV, 59% contacted a healthcare provider within 18 months of their results, 14% reported seeking HCV treatment, and only 8% reported receiving HCV treatment. Further, stimulant use, defined as methamphetamine, amphetamine, or cocaine use, is resurging. Polysubstance use of opioids and stimulants is increasing among rural PWID and is associated with increased factors for HCV transmission, such as syringe sharing. Yet, the effect of stimulant and polysubstance use on HCV testing and treatment remains unclear. The proposed research aims to reduce the morbidity and mortality associated with HCV among PWID in rural communities. The proposed project will leverage data collected in eight NIH-funded studies of the Rural Opioid Initiative (ROI) (NIDA U24DA048538). We will use this comprehensive collection of data and the integration of epidemiological and spatial methods to determine the effect of opioids, stimulants (methamphetamine, amphetamine, cocaine), and their simultaneous and concurrent use on HCV infection, testing, and treatment completion in rural communities included in the ROI infrastructure. Aim 1 will estimate the association of opioid use, stimulant use, and polysubstance use of opioids and stimulants with the presence of HCV infection among PWID. Aim 2 will measure the association of opioid, stimulant, and polysubstance (opioid and stimulant) use on HCV testing and treatment completion. Aim 3 will identify high-priority locations to target HCV testing and treatment among PWID communities within the ROI infrastructure. The results from this project will identify rural communities that require HCV testing and treatment support to curtail the spread of HCV and associated mortalities among PWID. This project will enhance the applicant’s expertise and application of epidemiological methods to solve public health issues in the fields of substance use and infectious diseases. The applicant will gain research, collaboration, and dissemination experience to prepare her for an independent epidemiological investigator career. This project and applicant are supported by distinguished faculty in epidemiology, substance use, infectious diseases, behavioral health, geography, population health, and public health informatics.