No one size fits all-Shortening duration of therapy with direct-acting antivirals for hepatitis C genotype 1 infection.

The advent of shorter duration, highly effective and well-tolerated interferon-free therapy now provides an opportunity for virtually all HCV-infected individuals to be cured. However, there continues to be a need to simplify and shorten treatment duration. Shortening therapy to 8 weeks with sofosbuvir and ledipasvir can be considered in treatment patients with HCV genotype 1 infection and low baseline viral load. A number of other 8-week dual and triple therapy direct-acting antiviral (DAA) regimens are in advanced clinical development. Several small studies have further demonstrated the feasibility of 6 weeks of sofosbuvir therapy in combination with an NS5A inhibitor and a protease inhibitor for HCV genotype 1. Four weeks of therapy with various combinations of the currently available DAAs appears to be suboptimal with poor response rates observed in phase 2 trials. Response-guided therapy is another promising tool that may allow for shorter therapy but require further research. Shortening therapy and retreating relapsers may be a viable cost-saving measure, but requires further cost-benefit analysis and more data on the impact of resistance on retreatment options.