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However, clinical experience suggests that, with appropriate infrastructure and patient support, including treatment of substance use disorders, HCV treatment is very feasible in this population.[5,6,7,8,9] Examples of patient support include directly-observed therapy and related approaches, patient navigation, and group treatment models, particularly in substance use disorder treatment settings.[10] HCV Treatment in Persons with Opioid Use Impact of Opioid Use on Natural History of HCV Through the sharing of syringes and other injection equipment, injection opioid use is a major driver of HCV transmission, but opioid use itself, either orally or by injection, does not appear to speed the progression of liver disease in persons with chronic HCV.[11] Opioid analgesic use disorder is also a risk factor for HCV acquisition and transmission, as some individuals transition from oral ingestion of prescribed opioids to use of illicit opioids, which can include injection opioid use.[12,13] Nevertheless, opioid use itself, either orally or by injection, does not appear to impact the natural history of liver disease in persons with chronic HCV.[11] Impact of Treating People with Active Injection Drug Use on HCV Transmission Mathematical modeling, even assuming a reinfection rate equal to initial infection rates, has demonstrated that HCV treatment among persons with active injection drug use would result in a significant reduction in HCV transmission.[14,15,16,17] Several studies utilizing mathematical modeling based on DAA regimens concluded that scaling up HCV treatment in people who inject drugs (PWID) would have a major impact in reducing HCV incidence and prevalence in this patient population, even more so in the setting of robust access to sterile injection equipment and medications for opioid use disorder (e.g., buprenorphine-naloxone or methadone).[16] Further, scaling up and widespread treatment of HCV in PWID as a prevention tool, akin to treating HIV to reduce community viral load, has become a more realistic goal with the short-course, well-tolerated oral regimens