title: Optimizing triple therapy and IFN/RBV-free regimens for hepatitis C virus infection.
abstract: Treatment of chronic hepatitis C virus infection has substantially improved following the advent of direct acting antiviral (DAA) agents. Although the first generation protease inhibitors telaprevir and boceprevir improved sustained viral response (SVR) rates, adverse events remain severe and immature termination of the therapy is frequent; however, intensive dose modification has improved completion and SVR rates. Interferon-free DAA combination therapies, such as asunaprevir and daclatasvir dual therapy are under development and promise higher SVR rates with fewer adverse events. Resistance monitoring and modification of DAA therapy based on pre-existing or de novo resistance variants should be considered. Future therapies are expected to have pan-genotypic activity with shorter duration and improved tolerability, even among cirrhotic and liver transplant patients.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Fukiko
authors.initials: F
authors.lastname: Mitsui
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D058990:Molecular Targeted Therapy; D011480:Protease Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; 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; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: NS5A inhibitor; direct-acting antiviral agents; polymerase inhibitor; protease inhibitor; sustained viral response