New direct-acting antiviral agents for the treatment of chronic hepatitis C in 2014

The development of direct-acting antiviral agents (DAA) against the hepatitis C virus (HCV) has seen enormous progress in recent years. In 2011, the first protease inhibitors boceprevir (BOC) and telaprevir (TLV) were approved, which still need to be combined with pegylated interferon alpha (PEG-IFN alpha) and ribavirin (RBV) and are used only in patients with genotype 1. With sofosbuvir (SOF) and simeprevir (SMV), two new DAA are available. More DAA are in clinical development. Which changes in the treatment of chronic hepatitis C infection can be expected with the approval of the new DAA in 2014? Relevant phase IIb and phase III studies for the approval in 2014 were considered for drugs approved by the FDA or EMA at the editorial deadline. For patients with genotype 1, the combination of SOF, SMV or faldaprevir with PEG-IFN alpha and RBV was successfully evaluated in phase III studies. In contrast to previous treatment with PEG-IFN alpha, RBV and telaprevir (TLV) or boceprevir (BOC), therapy can be shortened in most cases with a significantly improved side-effect profile. Cure rates above 80 % are possible. Data are also available for an interferon-free therapy with either SOF and RBV or SOF and SMV in GT-1 patients. SVR rates exceeding 60 % and up to 90 % are possible. However, treatment experience with these combinations is low and an unrestricted interferon-free therapy for genotype 1 should not be expected before 2015. For patients with genotypes 2 and 3, valid data for interferon-free therapies are available. The combination of SOF and RBV for 12 weeks in genotype 2 and 24 weeks for genotype 3 is effective and shows equal or superior cure rates with fewer side effects than the PEG-IFN alpha/RBV therapy. For patients with genotype 1, the duration of therapy can be further reduced with better side effect profile. In certain situations, therapy without PEG-IFN alpha is possible and should be considered. For patients with genotypes 2 and 3, an interferon-free therapy will be standard of care in 2014.