New Antivirals Show Promise for an Interferon-free Hepatitis C Treatment

Atif Zaman, MD, MPH


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In This Article

Abstract and Introduction


Patients with HCV genotype 1 and previous null response achieved a 36% sustained virologic response at 24 weeks of therapy with daclatasvir and asunaprevir alone.


The current generation of direct acting antivirals (DAAs), telaprevir and boceprevir, in combination with peginterferon and ribavirin (PEG/RBV) have demonstrated limited efficacy in patients with hepatitis C virus (HCV) genotype 1 infection who have experienced a previous null response to PEG/RBV. Sustained virologic response (SVR) has been approximately 30%, with associated high rates of resistance. Now, researchers have explored the efficacy of two next-generation DAAs with and without PEG/RBV in this patient population.

This phase IIa, industry-sponsored, randomized study involved 21 patients with previous null response to PEG/RBV (defined as <2 log HCV RNA drop from baseline at 12 weeks). Eleven patients received 60 mg daily of daclatasvir (an NS5A replication complex inhibitor) and 600 mg twice daily of asunaprevir (an NS3 protease inhibitor) for 24 weeks (DAA-only group). Ten patients received both DAAs and PEG/RBV for 24 weeks (DAA+PEG/RBV group). Of note, 90% of the study cohort had IL28B genotypes CT or TT, which respond poorly to PEG/RBV. The primary endpoint was SVR at 12 weeks after stopping therapy.

The SVR in the DAA-only group was 36% (2 of 9 with genotype 1a and 2 of 2 with genotype 1b). Six patients, all with genotype 1a, had viral breakthrough that was associated with viral resistance mutations to both DAAs. Alternately, the SVR in the DAA+PEG/RBV group was 100% (90% with genotype 1a) at 12 weeks after therapy and 90% at 24 weeks. Most adverse events were mild to moderate and included diarrhea, fatigue, headache, and nausea.


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