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New Regimens for Non-genotype 1 HCV Mono-infection Reported at ID Week 2013

Standard treatment for genotype 2 and 3 is ribavirin and peginterferon for 24 weeks because the currently available HCV protease inhibitors are less active against these genotypes. The combination of ribavirin and peginterferon with a directly-acting antiviral (DAA) active against these genotypes may improve response rates, allow for shorter courses of therapy or both. Daclatasvir (DCV) is a potent NS5A inhibitor with activity against HCV genotypes 2 and 3. The COMMAND study compared triple therapy with DCV, ribavirin and peginterferon for 12 or 16 weeks to standard treatment for genotype 2 or 3 infection. There were 151 treatment-naive, participants enrolled and approximately 25 patients with each genotype in each of the 3 treatment arms. Eighty-three percent in the two DCV arms had a protocol-defined response (HCV RNA <25 IU/mL at 4 weeks and undetectable at 10 weeks) and received the intended duration of triple therapy. The rest received 12 weeks of triple therapy and 12 weeks of ribavirin and peginterferon. For genotype 2, SVR24 rates for 12 and 16 weeks of triple therapy were 88% and 83%, respectively compared to 63 for standard treatment. For genotype 3 the corresponding SVR 24 rates were 69%, 70% and 59%. In the DCV arms, virologic failure was mostly due to relapse, which was more common with genotype 3, underlying cirrhosis or the presence of baseline resistance polymorphisms in the NS5A gene. Adverse events were frequent but very similar with DCV triple therapy and standard treatment. This study suggests triple therapy with DCV modestly increases SVR rates with a 12 week treatment course compared to 24 weeks of ribavirin and peginterferon. Genotype 3 is harder to cure and may require other approaches to reduce relapse and improve overall responses. Studies of combinations of pangenotypic DAAs will be of interest for genotype 3, which is emerging as the new hard to treat genotype in the era of DAAs developed primarily to treat genotype 1.

Dore G, Lawitz E, Hezode C et al. Daclatasvir Combined With Peginterferon Alfa-2a and Ribavirin for 12 or 16 Weeks in Patients With Hepatitis C Virus Genotype 2 or 3 Infection: COMMAND GT 2/3 Study. ID Week 2013, San Francisco, CA, October 2-6, 2013, abstract 1827.

Source: Reporting from San Francisco for PRN News: David H Shepp, MD