Project summary Since recent innovations in hepatitis C virus (HCV) treatment make it possible to eradicate HCV infection in nearly every individual, the World Health Organization is calling for global HCV elimination by 2030. Elimination means reducing incident infection by 90% and HCV-related mortality by 65% from a 2015 benchmark. However, a high incidence of new infections and reinfections from the expanding opioid epidemic and historic low HCV treatment uptake might threaten HCV elimination among people who inject drugs (PWID), the primary HCV risk group in the USA. In this grant we asking both whether targets are being met and which subpopulations are being left befind focusing on Baltimore PWID, especially those coinfected with HIV. For more than 25 years, we have investigated HIV, hepatitis C virus (HCV) and liver disease in a community-based cohort of PWID (called ALIVE) and now the cohort is the ideal setting to accomplish our aims which are: (1) to evaluate the trajectory of decline in HCV viremia among a community-based cohort of in- and out-of care PWID in the era of all oral HCV therapy and assess whether this trajectory differs for those who are HIV/HCV co-infected and HCV monoinfected; (2) to estimate the contribution of incidence, treatment, and reinfection to HCV viremia changes among HIV-infected and -uninfected Baltimore PWIDs; and (3) to assess the population impact of expanded HCV treatment on liver disease outcomes including progression and emergence of different types of liver disease in HIV-infected compared to uninfected PWID. We have detailed, longitudinal measures of liver disease in the ALIVE cohort. Now is the right time to accomplish these aims so that we can assess if Baltimore (and possibly other urban areas in the USA) are on track for HCV elimination and to help guide those future efforts in time to adjust public health practices to ensure the goals are met by 2030.