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.

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.