Virological escape in HCV genotype-1-infected patients receiving daclatasvir plus ribavirin and peginterferon alfa-2a or alfa-2b.

Background: Daclatasvir (DCV; BMS-790052) is a picomolar inhibitor of HCV non-structural protein 5A (NS5A) and has demonstrated efficacy in patients chronically infected with HCV.

Methods: In the double-blind, randomized studies AI444021 and AI444022, 71 Japanese patients chronically infected with HCV genotype 1 (predominantly genotype 1b) received DCV (10 mg or 60 mg) plus peginterferon alfa-2b or alfa-2a and ribavirin. Virological failure occurred in 14% (5/36) of treatment-naive patients and 54% (19/35) of prior alfa/ribavirin non-responders.

Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir.

Unlabelled: In a sentinel cohort, hepatitis C virus (HCV) patients (primarily genotype [GT] 1a) were treated with daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor). Preexistence, emergence, and persistence of resistance variants in patients who failed this treatment are described. HCV-infected null responders received daclatasvir (60 mg once daily) and asunaprevir (600 mg twice daily) alone (Group A, 11 patients) or with peginterferon alfa-2a and ribavirin (Group B, 10 patients) for 24 weeks.

Natural prevalence of NS5A polymorphisms in subjects infected with hepatitis C virus genotype 3 and their effects on the antiviral activity of NS5A inhibitors.

Background: Hepatitis C virus (HCV) NS5A replication complex inhibitors (RCIs) have been shown to exhibit picomolar antiviral activity against genotype 1 (GT1) in vitro. This has translated into rapid and robust declines in HCV RNA in GT1 patients. Less is known about the susceptibility of other genotypes such as GT3 to inhibition by NS5A RCIs.