Interferon-free, direct-acting antiviral therapy for chronic hepatitis C

J Viral Hepat. 2015 Nov;22(11):861-70. doi: 10.1111/jvh.12422. Epub 2015 Jun 17.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Antiviral Agents / administration & dosage*
  • Clinical Trials as Topic
  • Drug Therapy, Combination / methods
  • Enzyme Inhibitors / administration & dosage*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Viral Nonstructural Proteins / antagonists & inhibitors

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • NS3 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus