Impact of HCV protease-inhibitor-based triple therapy for chronic HCV genotype 1 infection

Boceprevir and telaprevir are the first HCV protease inhibitors to be approved for the treatment of chronic hepatitis C genotype 1 infection. These drugs must be used in combination with pegylated interferon plus ribavirin (P/R) to maximize efficacy and prevent the emergence of resistance-associated variants (RAVs). In randomized, placebo-controlled international studies in treatment-naive and previously treated HCV patients, treatment with either boceprevir- or telaprevir-based triple therapy regimens significantly increased sustained virological response rates compared with placebo plus P/R. Protease inhibitors have the potential, not only to significantly increase cure rates among patients with genotype 1 infection, but also to reduce the duration of treatment for patients who have an extended rapid virological response. Boceprevir is associated with an increased incidence of anaemia and dysgeusia and telaprevir is associated with an increased incidence of rash and anaemia. The emergence of RAVs was associated with an increased risk of virological failure in clinical studies. Although these new drugs bring significant promise, it remains unclear if all genotype 1 patients will need triple therapy. Here, we review some of the complexities uncovered and controversies highlighted by the introduction of HCV protease inhibitors.