title: Resistance of Hepatitis C Virus to Inhibitors: Complexity and Clinical Implications.
abstract: Selection of inhibitor-resistant viral mutants is universal for viruses that display quasi-species dynamics, and hepatitis C virus (HCV) is no exception. Here we review recent results on drug resistance in HCV, with emphasis on resistance to the newly-developed, directly-acting antiviral agents, as they are increasingly employed in the clinic. We put the experimental observations in the context of quasi-species dynamics, in particular what the genetic and phenotypic barriers to resistance mean in terms of exploration of sequence space while HCV replicates in the liver of infected patients or in cell culture. Strategies to diminish the probability of viral breakthrough during treatment are briefly outlined.
authors.affiliation: Liver Unit, Internal Medicine, Laboratory of Malalties Hepàtiques, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain. celia.perales@vhir.org.|Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain. celia.perales@vhir.org.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08035 Barcelona, Spain. celia.perales@vhir.org.
authors.forename: Celia
authors.initials: C
authors.lastname: Perales
authors.affiliation: Liver Unit, Internal Medicine, Laboratory of Malalties Hepàtiques, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain. josep.quer@vhir.org.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08035 Barcelona, Spain. josep.quer@vhir.org.|Universitat Autònoma de Barcelona, Bellaterra 08193, Spain. josep.quer@vhir.org.
authors.forename: Josep
authors.initials: J
authors.lastname: Quer
authors.affiliation: Liver Unit, Internal Medicine, Laboratory of Malalties Hepàtiques, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain. josep.gregori@vhir.org.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08035 Barcelona, Spain. josep.gregori@vhir.org.|Roche Diagnostics SL, 08174 Sant Cugat del Vallès, Spain. josep.gregori@vhir.org.
authors.forename: Josep
authors.initials: J
authors.lastname: Gregori
authors.affiliation: Liver Unit, Internal Medicine, Laboratory of Malalties Hepàtiques, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain. jignacio.esteban@ciberehd.org.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08035 Barcelona, Spain. jignacio.esteban@ciberehd.org.|Universitat Autònoma de Barcelona, Bellaterra 08193, Spain. jignacio.esteban@ciberehd.org.
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Esteban
authors.affiliation: Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain. edomingo@cbm.csic.es.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08035 Barcelona, Spain. edomingo@cbm.csic.es.
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D010641:Phenotype
chemical_list: D000998:Antiviral Agents
keywords: antiviral treatment; hepatitis C virus; viral quasi-species; viral resistance