title: Hepatitis C virus resistance to the new direct-acting antivirals.
abstract: BACKGROUND
  The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs).
  
  
  METHODS
  Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted.
  
  
  CONCLUSIONS
  Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.
authors.affiliation: a Infectious Diseases Unit , IdiPAZ & La Paz University Hospital , Madrid , Spain.
authors.forename: Isabella
authors.initials: I
authors.lastname: Esposito
authors.affiliation: b Instituto de Ciencias Básicas y Medicina Experimental (ICBME) , Instituto Universitario del Hospital Italiano de Buenos Aires , Buenos Aires , Argentina.|c Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Buenos Aires , Argentina.
authors.forename: Julieta
authors.initials: J
authors.lastname: Trinks
authors.affiliation: a Infectious Diseases Unit , IdiPAZ & La Paz University Hospital , Madrid , Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D017211:Treatment Failure; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents
keywords: Drug resistance; HCV; NS5A inhibitors; resistance testing; simeprevir; sofosbuvir