Simeprevir versus telaprevir in combination with pegylated interferon and ribavirin in HCV genotype 1-infected patients: the Phase III ATTAIN study

replaced by alternative therapies, although many regions of the world are only now starting to utilize telaprevir and boceprevir triple therapies and will likely continue using other interferon-based regimens for some time. The combination of the nucleoside analogue, sofosbuvir, with peginterferon and ribavirin administered for 12 weeks has yielded high rates of sustained virological response for genotype 1 and was approved by regulatory agencies in the US and Europe in 2013. Rates of SVR were generally similar across all subpopulations, although patients with cirrhosis had lower rates of SVR. This regimen is considered the treatment of choice for patients with genotype 1 contemplating interferon-based therapy, according to recent treatment recommendations from AASLD/IDSA and EASL. The treatment recommendations also suggest that triple therapy with simeprevir, a second generation protease inhibitor also recently approved by regulatory authorities, can be considered as alternate therapy for patients with genotype 1 who can tolerate an interferon-based regimen. Combination of simeprevir with peginterferon and ribavirin achieved significantly higher rates of sustained virological response (SVR) compared to peginterferon and ribavirin alone in patents treated for 24–48 weeks. Patients with cirrhosis also had lower rates of SVR compared to non-cirrhotics. This regimen is specifically not recommended for patients with genotype 1a with baseline Q80K polymorphism due to the substantially lower rate of SVR. The EASL guidelines also indicate that combination of peginterferon, ribavirin, and daclatasvir (NS5A inhibitor) may be used to treat HCV specifically genotype 1b in the EU. This drug is currently not available in the U.S. The future role of peginterferon-based regimens will likely depend on many factors which will be specific to different geographic regions of the world, including cost-effectiveness, frequency of favorable IL28B genotype, and accessibility of newer DAA regimens.