title: Mechanisms of Virologic Failure with Direct-Acting Antivirals in Hepatitis C and Strategies for Retreatment.
abstract: The current standard of care for hepatitis C therapy is the combination of direct-acting antiviral (DAA) agents. These orally administered medications target the viral proteins and halt the hepatitis C virus lifecycle. Despite high cure rates with these novel drugs, virologic failure with DAAs are of mounting concern as real-world sustained virologic response 12 rates seem lower than expected. The mechanisms of virologic failure to DAAs are likely multifactorial, including baseline resistance variants, the efficacy of the agents used, and host factors. Salvage therapy for DAA virologic failures is an area of emerging research.
authors.affiliation: Department of Hepatology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Costilla
authors.affiliation: Department of Hepatology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Mathur
authors.affiliation: Department of Hepatology, The Texas Liver Institute, University of Texas Health Science Center at San Antonio, 607 Camden, San Antonio, TX 78215, USA. Electronic address: Gutierrezj8@uthscsa.edu.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Gutierrez
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000096:biosynthesis; D012008:Recurrence; D019233:Retreatment; D000069474:Sofosbuvir / Q000627:therapeutic use; D017211:Treatment Failure; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D011480:Protease Inhibitors; D012367:RNA, Viral; D000069474:Sofosbuvir; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Direct-acting antivirals (DAAs); Genotype 1; Hepatitis C; NS5A inhibitor; Protease inhibitor; RNA-polymerase inhibitor; Resistance-associated variants (RAVs); Retreatment