Review of direct-acting antiviral agents for the treatment of chronic hepatitis C

Expert Opin Investig Drugs.

Review

Posted online on June 4, 2013. (doi:10.1517/13543784.2013.806482)

Nihar Shah ^†1 MD Fellow in Hepatology, Tracey Pierce ² BA Clinical Research Coordinator & Kris V Kowdley ³ MD FACP Director

¹ Digestive Disease Institute, Virginia Mason Medical Center,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA +1 206 223 2319; +1 206 341 1188; kris.kowdley@vmmc.org

² Digestive Disease Institute, Virginia Mason Medical Center,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA

³ Digestive Disease Institute, Virginia Mason Medical Center, Liver Center of Excellence,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA

^†Author for correspondence

Introduction: Rapid breakthroughs in the treatment of hepatitis C virus (HCV) infection have dramatically altered the treatment landscape for this chronic disease. In 2011, the protease inhibitors (PIs) boceprevir and telaprevir in combination with peginterferon (peg-IFN) and ribavirin (RBV) were the first direct-acting antivirals (DAAs) approved in the United States for treatment of genotype (GT) 1 HCV. Several DAAs currently in late-stage clinical trials, including NS3/NS4A serine PIs, NS5A inhibitors, NS5B polymerase inhibitors (both nucleoside and non-nucleoside) and cyclophilin inhibitors, both with and without peg-IFN and RBV, are promising for the treatment of HCV. DAA regimens offer several advantages including that they specifically target HCV viral replication and thus appear to be less dependent on host characteristics, very high SVR rates accompanied by fewer side effects (SE) and lower pill burdens. A review on the treatment of HCV is important and timely as the development on DAAs is progressing rapidly and the health-care providers need to be aware about this as these regimens are anticipated to become clinically available soon.

Areas covered: The literature was searched and reviewed using PubMed as well as data gathered from those presented at the international liver meetings, AASLD and EASL as well as CROI.

Expert opinion: With the potential of eliminating IFN and RBV, several DAAs under clinical development appear to be promising using novel approaches with good antiviral effects, shorter duration and lower SE profile.

Keywords

ABT-267, ABT-333, ABT-450, asunaprevir, boceprevir, cirrhosis, cyclophilin inhibitors, daclatasvir, danoprevir, directly acting antiviral agents, faldaprevir, hepatitis C virus, ledipasvir, mericitabine, NS5A inhibitors, NS5B polymerase inhibitors, null responders, partial responders, pegylated interferon, protease inhibitors, relapsers, resistance, ribavirin, simeprevir, sofosbuvir, SVR, telaprevir, treatment naïve

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