title: New developments in HCV therapy.
abstract: About half of the patients with chronic hepatitis C are still not cured by treatment with the current standard of care, peginterferon α/ribavirin. Direct antiviral drugs may overcome the limitations of standard antiviral therapy. The most promising new agents are inhibitors of the NS3/4A protease, the NS5B polymerase and the NS5A protein. Several compounds against these targets have entered clinical evaluation. Early clinical trials have emphasized the high potential for selecting resistant Hepatitis C virus variants. Furthermore, development of several new direct antivirals was stopped because of concerns over tolerability and safety. Then, in 2010, two phase III trials with the NS3/4A protease inhibitors boceprevir (SPRINT-2) and telaprevir (ADVANCE) showed that the combination of these compounds with standard care increases sustained virologic response rates in treatment-naïve genotype 1 patients from 38-44% to 66-75%. Future goals of therapy with direct antiviral agents are to improve tolerability, shorten the duration of therapy and overcome the issue of resistance. Several studies have been initiated that combine different novel therapies, with and without interferon α/ribavirin.
authors.affiliation: Department of Internal Medicine 1, Hospital of the Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kronenberger
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011392:Proline; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; 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