University of Ottawa, Division of Infectious Diseases, Ottawa, Canada.
Development of more effective hepatitis C (HCV) antivirals has been rapid. The addition of orally administered medications that target virus [Direct Acting Antivirals (DAA)] to pegylated interferon and ribavirin have dramatically increased sustained virologic response rates in genotype 1-infected patients. However, the side effect profile remains challenging and the dosing schedule complicated. DAAs currently in development possess the promise of once or twice daily dosing schedules, improved tolerance profiles, higher resistance barriers and pan-genotypic antiviral activity. Emerging interferon-sparing, combination DAA data demonstrates that interferon is not essential to achieve sustained virological response. This will expand the proportion of HCV-infected patients who can be considered for therapy and will allow for better tolerated regimens. Expertise in HCV antiviral resistance, drug metabolism and drug-drug interactions, and optimization of drug adherence are now key requirements in the DAA era.