Hepatitis C virus (HCV) infection affects about 160 million people worldwide. Currently, it is treated with pegylated
interferon (PEG-IFN) plus ribavirin, associated with a protease inhibitor in case of genotype 1 infection. However,
this combination is often contraindicated and associated with severe adverse events that limit its use in clinical practice.
Several drugs active against HCV are in an advanced phase of clinical development. Among these, sofosbuvir appears one
of the most promising candidates for use in association with both interferon and interferon-free combinations. This review
focuses on the results of several sofosbuvir-based phase III trials that have very recently become available. These studies
show that the co-administration of sofosbuvir, PEG-IFN and ribavirin for 12 weeks is associated with a very high rate of
sustained virological responses (SVR) (about 90%) in naïve patients with genotypes 1, 4, 5 or 6. In patients infected by
genotypes 2 or 3, the interferon-free combination of sofosbuvir and ribavirin administered for 12 weeks is associated with
a SVR of 97% and 56% in naïve patients, and of 86% and 30% in experienced genotype 2 or 3 patients, respectively. The
safety and tolerability profile is optimal and consistent with that of the other drugs administered in the combination (ribavirin
and/or interferon). In conclusion, the recent phase III trials of sofosbuvir confirm the excellent results of phase II
studies in terms of efficacy and safety and will probably open a new era in the fight against HCV.
HCV, interferon, interferon-free combination, polymerase inhibitors, randomized clinical trial, sofosbuvir.
Department of Clinical Medicine and Surgery (Ed. 18), University of Naples “Federico II”, via S. Pansini 5, I-80131 Naples, Italy.