Hepatitis C virus (HCV) infection is one of the main causes of liver disease worldwide. Its treatment is currently
based on the combination of peg-interferon, ribavirin, and, for patients with genotype 1, a protease inhibitor (telaprevir
or boceprevir). However, interferon-based combinations are not effective in all patients. Moreover, they are contraindicated
in patients who cannot receive interferon (e.g. those with decompensated cirrhosis), and are frequently associated
with adverse events. Consequently, there is a need to develop new drugs to treat HCV infection. This review focuses
on preclinical and clinical data regarding sofosbuvir (GS-7977), a uridine nucleotide analogue inhibitor of HCV NS5 B
polymerase that is effective against HCV genotypes 1,2, 3,4 and 6. Thanks to its excellent pharmacokinetic profile, sofosbuvir
can be administered in an oral single daily dose. In vitro it exerts a potent antiviral effect against HCV. Clinical data
show that combined with peg-interferon and ribavirin for 12 weeks it yields SVR of about 90% in subjects with HCV
genotype 1 and about 100% in patients with HCV genotype 2 or 3. Moreover, sofosbuvir and ribavirin administered for 12
weeks yield similar high SVR rate (84% for genotype 1 and 100% for genotype 2/3 patients) as well as sofosbuvir and daclatasvir
(an inhibitor of NS5A) which produce SVR rate of about 100% regardless of genotype or of ribavirin employment.
Safety and tolerability of sofosbuvir appear to be excellent. In conclusion, sofosbuvir especially in interferon-free
combinations represents a very promising option in the treatment of chronic hepatitis C.
Keywords: Clinical trial, combination therapy, hepatitis C virus, pegylated-interferon, polymerase inhibitors, resistance, ribavirin,
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