title: Telaprevir: a promising protease inhibitor for the treatment of hepatitis C virus infection.
abstract: Chronic hepatitis C affects 130,000,000 people worldwide. Hepatitis C virus (HCV) is a single-strand RNA virus responsible for most cases of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) in the Western world. The gold standard for the treatment of chronic hepatitis C (combination of pegylated-interferon alpha and ribavirin) results in a sustained virological response (namely, clearance of serum HCV RNA 6 months after therapy withdrawal) in only about half treated patients. Therefore, there is a race to develop new drugs for the treatment of HCV infection. One of the most promising approaches is to use protease inhibitors, i.e. drugs inhibiting NS3/NS4A HCV protease, which plays a crucial role in the viral life cycle. Telaprevir (VX-950) is the protease inhibitor in the most advanced phase of clinical testing. Telaprevir is orally available and when used in monotherapy it induced a median decline of 4 logs of HCV RNA after two weeks of therapy. However, mutants with a lower sensitivity to telaprevir have been demonstrated in a high proportion of patients within 14 days of monotherapy. The drug has been used in clinical trials in combination with pegylated-interferon and ribavirin. This triple combination resulted in a higher rate of SVR but also in a higher rate of side effects (rash, gastrointestinal disorders, and anemia) than standard treatment. This review focuses on the mechanism of action, pharmacokinetics, clinical efficacy, and tolerability of telaprevir, and on possible use of this drug in combination with other drugs for the treatment of HCV infection.
authors.affiliation: Dipartimento di Medicina Pubblica e Sicurezza Sociale - Sezione di Malattie Infettive, Universită di Napoli "Federico II", Italy.
authors.forename: I
authors.initials: I
authors.lastname: Gentile
authors.forename: C
authors.initials: C
authors.lastname: Viola
authors.forename: F
authors.initials: F
authors.lastname: Borgia
authors.forename: G
authors.initials: G
authors.lastname: Castaldo
authors.forename: G
authors.initials: G
authors.lastname: Borgia
mesh_terms: D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; C486464:telaprevir