The successful scale-up of direct-acting antiviral hepatitis C treatments will benefit from concerted investments in implementation science.

The introduction of highly efficacious direct-acting antiviral (DAA) treatment therapeutics presents new opportunities to both directly reduce chronic hepatitis C virus (HCV) prevalence and prevent the onward transmission of HCV. To achieve the equitable scale-up of DAA interventions at the population level, however, reductions in HCV incidence and prevalence must be achieved among entire populations of people living with HCV-all in "real-world" conditions. In this commentary, we describe five problem areas that will benefit from new investments in implementation science in order to inform the scale-up of DAA interventions: (1) New evidence is needed to optimize the integration of DAA treatments into generalist models of care; (2) DAA scale-up needs to be adaptive to the needs of highly diverse and large populations living with HCV who will benefit from DAA interventions; (3) we need to do better at measuring and responding to features of implementation context; (4) costs need to be explicitly assessed in "real time"; and (5) new research-community-practice partnerships are needed to inform evolving HCV testing, treatment and prevention guidelines, policies, and programs. We offer solutions to address these problem areas, with an emphasis on describing how investments in implementation science can address each of these challenges "head on."