Aids Weekly Plus
Researchers in an open-label, phase 2a study administered 24 weeks of dual oral treatment of 60 mg NSFA replication complex inhibitor daclatasvir (DCV) once daily and 200 mg NS3 protease inhibitor asunaprevir (ASV) twice daily to 43 Japanese patients aged 20 to 75 years with chronic hepatitis C virus (HCV) genotype 1b. Of the 43 participants, 21 were null responders and 22 patients were not eligible for or could not tolerate standard therapy with pegylated interferon alfa and ribavirin.
At four weeks, more patients in the intolerant/ineligible groups had achieved undetectable HCV RNA levels than null responders. After eight weeks, all participants had undetectable HCV RNA levels. Sustained virologic response occurred in 76.7 percent of the cohort at 12 and 24 weeks; there was 90.5 percent in null responders and 63.6 percent in the intolerant/ineligible participants. Virologic breakthrough occurred in three intolerant/ineligible participants with four relapses after treatment. No null responders had a relapse or virologic breakthrough. Researchers observed no associations between breakthrough or relapse and factors, including gender, IL28B genotype, age, HCV RNA level at baseline, stage of fibrosis, and reasons for treatment ineligibility. Adverse events were mild. They included headache, nasopharyngitis, diarrhea, and increased ALT/AST. Five patients experienced serious events and three discontinued use due to elevated hyperbilirubinemia or transaminase.
The researchers concluded that dual oral therapy with daclatasvir and asunaprevir produced rapid clearance of detectable HCV RNA and achieved high rates of sustained virologic response in two groups of difficult-to-treat patients. These results confirmed initial findings that HCV genotype 1b infections can be cured with daclatasvir and asunaprevir, without pegylated interferon-alfa and ribavirin. The researchers acknowledged that further research is needed to assess the benefits of this and other combinations in larger and more diverse patient groups.
The full report, “Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options” was published in the Journal of Hepatology (2013; 58 (4): 655-662).