title: New treatments for chronic hepatitis C virus infection.
abstract: The treatment of hepatitis C virus infection (HCV) by a combination of pegylated interferon and ribavirin, according to early viral kinetics, leads to a sustained virological response (SVR) in more than 50% of patients with chronic infection. This SVR is a complete recovery of the infection but more than 50% of genotype 1-infected patients do not achieve SVR. A better understanding of the viral cycle, and the characterization of viral enzymes which are potential targets, resulted in the development of new molecules, direct acting antivirals (DAA) targeted against HCV, either specific of genotype 1 (protease inhibitors NS3/NS4A and polymerase inhibitors NS5B) or with a wider spectrum (NS5A or entry inhibitors), and non-specific antivirals (new interferons, cyclophilin inhibitors). We describe the results of phase II and III trials which clearly demonstrated a 20 to 30% increase in the SVR rate of genotype 1-infected patients, either naïve or treatment experienced. These new drugs should be approved by the end of 2011, after a temporary approval for compassionate use in cirrhotic patients with previous relapse or partial response to the combination therapy. In the future, the main limitations of triple therapy will be safety (cutaneous rash or anemia which may be controlled), cost, compliance, viral resistance, and drug interactions that must be avoided by educating patients and physicians.
authors.affiliation: Unité d'hépatologie, hôpital Cochin, université Paris-Descartes, AP-HP, Inserm U-1016, 27, institut Cochin, rue du Faubourg-Saint-Jacques, 75679 Paris cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Corouge
authors.forename: S
authors.initials: S
authors.lastname: Pol
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D057176:Compassionate Use Trials; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D035703:Therapies, Investigational
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; D012324:RNA-Dependent RNA Polymerase; C100416:peginterferon alfa-2a