title: Prevention and management of treatment failure to new oral hepatitis C drugs.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection has become a curable disease. Sustained virologic response rates above 90% have been achieved with recommended direct-acting antiviral (DAA) combinations in most registration trials. However, outcomes in real-world patients are lower. In patients experiencing DAA failure, resistance-associated variants (RAVs) are almost universally selected. At this time it is unclear when and how to re-treat hepatitis C in patients with prior DAA failure.
  
  
  METHODS
  The rate of DAA failure and predictors of lack of treatment response using distinct DAA combinations are analyzed. We discuss the management of HCV treatment failure and the impact of RAVs on re-treatment strategies.
  
  
  CONCLUSIONS
  Failure to DAA combinations occurs more often in chronic hepatitis C patients with baseline predictors of poor response, such as those with RAVs, genotypes 3 or 1a, advanced liver cirrhosis, elevated serum HCV-RNA and perhaps HIV coinfection. Impaired antiviral efficacy is more frequent when multiple factors are present. On-treatment predictors of DAA failure are poor drug adherence and development of side effects. Extending the length of therapy, adding ribavirin and/or using DAA from other drug families may allow successful re-treatment of most prior DAA failures.
authors.affiliation: a Department of Internal Medicine , Puerta de Hierro Research Institute & University Hospital , Majadahonda , Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Benítez-Gutiérrez
authors.affiliation: b Infectious Diseases Unit , La Paz University Hospital , Madrid , Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
authors.affiliation: c Department of Internal Medicine , La Milagrosa Clinic , Madrid , Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.affiliation: a Department of Internal Medicine , Puerta de Hierro Research Institute & University Hospital , Majadahonda , Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.affiliation: d Department of Infectious Diseases , University Hospital Crosshouse , Kilmarnock , Scotland , United Kingdom.
authors.forename: José V
authors.initials: JV
authors.lastname: Fernandez-Montero
authors.affiliation: a Department of Internal Medicine , Puerta de Hierro Research Institute & University Hospital , Majadahonda , Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Arias
authors.affiliation: b Infectious Diseases Unit , La Paz University Hospital , Madrid , Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Peña
authors.affiliation: b Infectious Diseases Unit , La Paz University Hospital , Madrid , Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage*; D060085:Coinfection; D024882:Drug Resistance, Viral / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000379:methods; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy; D011379:Prognosis; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents
keywords: Hepatitis C; daclatasvir; drug resistance; paritaprevir; simeprevir; sofosbuvir; treatment failure