title: Prevalence of hepatitis C virus (HCV) variants resistant to NS5A inhibitors in naïve patients infected with HCV genotype 1 in Tunisia.
abstract: BACKGROUND
  Hepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitors have been recently developed to inhibit NS5A activities and have been approved for the treatment of HCV infection. However the drawback of these direct acting antivirals (DAAs) is the emergence of resistance mutations. The prevalence of such mutations conferring resistance to HCV-NS5A inhibitors before treatment has not been investigated so far in the Tunisian population. The aim of this study was to detect HCV variants resistant to HCV-NS5A inhibitors in hepatitis C patients infected with HCV genotype 1 before any treatment with NS5A inhibitors.
  
  
  METHODS
  Amplification and direct sequencing of the HCV NS5A region was carried out on 112 samples from 149 untreated patients.
  
  
  RESULTS
  In genotype 1a strains, amino acid substitutions conferring resistance to NS5A inhibitors (M28V) were detected in 1/7 (14.2 %) HCV NS5A sequences analyzed. In genotype 1b, resistance mutations in the NS5A region (R30Q; L31M; P58S and Y93H) were observed in 17/105 (16.2 %) HCV NS5A sequences analyzed. R30Q and Y93H (n = 6; 5.7 %) predominated over P58S (n = 4; 3.8 %) and L31M (n = 3; 2.8 %).
  
  
  CONCLUSIONS
  Mutations conferring resistance to HCV NS5A inhibitors are frequent in treatment-naïve Tunisian patients infected with HCV genotype 1b. Their influence in the context of DAA therapies has not been fully investigated and should be taken into consideration.
authors.affiliation: LR11-IPT-09, Epidémiologie et diversité génétique des virus hépatiques et entériques humains, Institut Pasteur de Tunis, 13 Place Pasteur, 1002, Tunis Belvédère, Tunisia. jamel.larous@gmail.com.|CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France. jamel.larous@gmail.com.|Virology Laboratory, Bordeaux University Hospital, Bordeaux, France. jamel.larous@gmail.com.
authors.forename: Jameleddine
authors.initials: J
authors.lastname: Aissa Larousse
authors.affiliation: CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France. pascale.trimoulet@chu-bordeaux.fr.|Virology Laboratory, Bordeaux University Hospital, Bordeaux, France. pascale.trimoulet@chu-bordeaux.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Trimoulet
authors.affiliation: CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France. patricia.recordon-pinson@u-bordeaux2.fr.|Virology Laboratory, Bordeaux University Hospital, Bordeaux, France. patricia.recordon-pinson@u-bordeaux2.fr.
authors.forename: Patricia
authors.initials: P
authors.lastname: Recordon Pinson
authors.affiliation: Virology Laboratory, Bordeaux University Hospital, Bordeaux, France. brigitte.tauzin@chu-bordeaux.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Tauzin
authors.affiliation: Department of Gastroenterology, Hospital of Tahar Maamouri, Nabeul, Tunisia. mm.azouz@rns.tn.
authors.forename: Mohamed Mssadak
authors.initials: MM
authors.lastname: Azzouz
authors.affiliation: Department of Gastroenterology B, La Rabta Hospital, Tunis, Tunisia. nabyl.benmami@rns.tn.
authors.forename: Nabyl
authors.initials: N
authors.lastname: Ben Mami
authors.affiliation: Department of Gastroenterology, Habib Bougatfa Hospital, Bizerte, Tunisia. imed.cheikh@rns.tn.
authors.forename: Imed
authors.initials: I
authors.lastname: Cheikh
authors.affiliation: LR11-IPT-09, Epidémiologie et diversité génétique des virus hépatiques et entériques humains, Institut Pasteur de Tunis, 13 Place Pasteur, 1002, Tunis Belvédère, Tunisia. henda.triki@pasteur.rns.tn.
authors.forename: Henda
authors.initials: H
authors.lastname: Triki
authors.affiliation: CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France. herve.fleury@viro.u-bordeaux2.fr.|Virology Laboratory, Bordeaux University Hospital, Bordeaux, France. herve.fleury@viro.u-bordeaux2.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Fleury
mesh_terms: D024882:Drug Resistance, Viral; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000302:isolation & purification; D006526:Hepatitis C / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015995:Prevalence; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D014416:Tunisia / Q000453:epidemiology; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase