Current prospects for interferon‐free treatment of hepatitis C in 2012

Present interferon‐based therapy for chronic hepatitis C is limited by both efficacy and tolerability. Telaprevir and boceprevir are the first two direct‐acting antiviral drugs (DAAs) that inhibit hepatitis C virus replication to be licensed for use in conjunction with pegylated interferon and ribavirin. Numerous other DAAs are in clinical development, and phases 2 and 3 trials are evaluating interferon‐free combination DAA therapy. Interferon‐free sustained virologic responses 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 hepatitis C virus is now finally becoming a reality.