Gastroenterologist and Hepatologist/Clinical Pharmacologist, Christchurch Hospital, Private Bag 4710, Christchurch, 8140, New Zealand. Catherine.firstname.lastname@example.org.
Present interferon-based therapy for chronic hepatitis C (CHC) is limited by both efficacy and tolerability. Telaprevir and boceprevir are the first two direct acting antiviral drugs (DAAs) which inhibit HCV replication to be licensed for use, in conjunction with pegylated interferon and ribavirin. Numerous other DAAs are in clinical development, and phase 2 and 3 trials are evaluating interferon-free combination DAA therapy. Interferon-free sustained virological responses (SVR) have now been achieved with combinations of asunaprevir and daclatasvir, sofosbuvir and ribavirin, sofosbuvir and daclatasvir, faldaprevir and BI207127, ABT-450, ritonovir and ABT-333, ABT-450, ritonovir and ABT-072, miracitabine, danoprevir and ritonavir, and alisporivir and ribavirin. Some drugs are genotype-specific in their activity, whereas others are pan-genotypic, and differential responses for the genotype 1 subtypes 1a and 1b have emerged with many DAA combinations. Viral breakthrough and resistance are important considerations for future trial design. The prospect of interferon-free combination DAA therapy for HCV is now finally becoming a reality.