title: Current prospects for interferon-free treatment of hepatitis C in 2012.
abstract: 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.
authors.affiliation: Christchurch Hospital, Christchurch, New Zealand. Catherine.stedman@cdhb.health.nz
authors.forename: Catherine A M
authors.initials: CA
authors.lastname: Stedman
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D021983:Cyclophilins / Q000037:antagonists & inhibitors; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D021983:Cyclophilins; D004791:Enzyme Inhibitors; D007372:Interferons; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase