Antimicrob Agents Chemother. 2013 Dec 2. [Epub ahead of print]
Auckland Clinical Studies, Auckland, New Zealand.
Background & Aims: Danoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a/ribavirin in treatment-naive HCV genotype (G)1-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a/ribavirin in G1 prior peginterferon/ribavirin null responders.Methods: Null responders (<2-log10 reduction in HCV RNA at week 12) were given open-label DNVr 100/100 mg q12h + peginterferon alfa-2a/ribavirin for 12 weeks. All patients achieving an early virologic response (EVR; ≥2-log10 decrease in HCV RNA by week 12) continued treatment with peginterferon alfa-2a/ribavirin; those without an EVR discontinued all study drugs.Results: Twenty-four prior null responders were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) with G1a. 96% of patients had an IL28B non-CC genotype. An SVR24 was achieved in 67% of patients, with a higher rate in G1b-infected (88%) vs. G1a-infected (25%) patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated. Two patients withdrew prematurely from study medications due to adverse events. Two serious adverse events were reported; both occurred after completion of DNVr therapy and were considered unrelated to treatment. No Grade 3/4 ALT elevations were observed.Conclusions: DNVr plus peginterferon alfa-2a/ribavirin demonstrated high SVR24 rates in HCV G1b prior null responders and was well tolerated.
PMID: 24295986 [PubMed - as supplied by publisher]