title: NS5A Resistance: Clinical Implications and Treatment Possibilities.
abstract: Treatments with interferon-free direct-acting antiviral agents have high efficacy, with sustained virological response rates of more than 90%. Nevertheless, they fail to eliminate the infection in 1-7% of patients. The majority of virological failures are due to relapse following treatment discontinuation, while virological rebound during therapy is rare. Although not the only factor, the presence of resistance-associated variants is one of the major causes for said failure. Resistance-associated variants affect the sequence involved in protein synthesis on which different direct-acting antiviral agents act (NS3/4A, NS5A, NS5B). Of all these variants, the ones with the greatest impact are resistance-associated variants that affect the NS5A region due to their long-term persistence. In this article we will describe the most significant NS5A resistance-associated variants, the clinical relevance of their detection both before and after treatment, their persistence over time, and lastly, we will devote particular attention to discussing what approach to adopt when dealing with treatment failure to an antiviral regimen that includes NS5A inhibitors.
authors.affiliation: Gastroenterology and Hepatology Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Santander, Spain; Infection, Immunity and Digestive Disease Group, Marqués de Valdecilla Research Institute (IDIVAL), Santander, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Llerena
authors.affiliation: Gastroenterology and Hepatology Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
authors.forename: Christie
authors.initials: C
authors.lastname: Perelló
authors.affiliation: Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Santander, Spain; Infection, Immunity and Digestive Disease Group, Marqués de Valdecilla Research Institute (IDIVAL), Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
mesh_terms: D000813:Anilides / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D002219:Carbamates / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005449:Fluorenes / Q000627:therapeutic use; D014644:Genetic Variation; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D011392:Proline; D011759:Pyrrolidines; D000069616:Simeprevir / Q000627:therapeutic use; D017211:Treatment Failure; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D011392:Proline; D011759:Pyrrolidines; D000069616:Simeprevir; D014633:Valine; D017361:Viral Nonstructural Proteins; C586541:ledipasvir; C586094:ombitasvir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir