title: Interferon-free, direct-acting antiviral therapy for chronic hepatitis C.
abstract: The treatment environment for chronic hepatitis C has undergone a revolution, particularly in genotype 1. Gone are interferon-based therapy and its associated tolerability challenges, inadequate response rates and numerous baseline factors that affect response to therapy. New and emerging treatment regimens employ all-oral combinations of direct-acting antiviral agents, and results of clinical trials suggest that these regimens routinely achieve cure rates >90%, even in patients who failed prior interferon-based triple therapy. In 2015, three all-oral FDA-approved regiments will be available for genotype 1 (sofosbuvir /ledipasvir, sofosbuvir/simeprevir, and paritaprevir/r/ombitasvir/dasabuvir). Furthermore, new treatment combinations appear to be more tolerable and require shorter duration of therapy. We provide an overview of the classes of direct-acting antiviral agents (DAAs), the clinical factors affecting their integration into combination therapies and recent findings from trials of such combination therapies in patients with genotype 1 HCV infection.
authors.affiliation: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Gutierrez
authors.affiliation: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lawitz
authors.affiliation: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: F
authors.initials: F
authors.lastname: Poordad
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; 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; D004791:Enzyme Inhibitors; 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
keywords: GS-9669; NS5A inhibitor; RNA polymerase inhibitor; asunaprevir; beclabuvir; daclatasvir; dasabuvir; direct-acting antivirals; elbasvir; faldaprevir; genotype 1; grazoprevir; hepatitis C; ledipasvir; ombitasvir; paritaprevir; protease inhibitor; resistance-associated variants; ribavirin; simeprevir; sofosbuvir