title: Hepatitis C virus (HCV) protease variability and anti-HCV protease inhibitor resistance in HIV/HCV-coinfected patients.
abstract: OBJECTIVE
  Data on the natural selection of isolates harbouring mutations within the NS3 protease, conferring resistance to hepatitis C virus (HCV) protease inhibitors (PIs), are limited for HIV/HCV-coinfected patients. The aim of this study was to describe the natural prevalence of mutations conferring resistance to HCV PIs in HIV/HCV-coinfected patients compared with HCV-monoinfected patients.
  
  
  METHODS
  The natural prevalences of HCV PI resistance mutations in 120 sequences from HIV/HCV-coinfected patients (58 genotype 1a, 18 genotype 1b and 44 genotype 4) and 501 sequences from HCV-monoinfected patients (476 genotype 1 and 25 genotype 4), retrieved from GenBank as a control group, were compared.
  
  
  RESULTS
  Of 76 sequences from HIV/HCV genotype 1-coinfected patients, six (7.9%) showed amino acid substitutions associated with HCV PI resistance (V36L, n=1; V36M, n=2; T54S, n=2; R155K, n=1). In 31 of 476 (6.5%) HCV genotype 1 sequences retrieved from the GenBank database, HCV PI resistance mutations were found. The difference was not statistically significant (P=0.6). All of the sequences from HIV/HCV genotype 4-coinfected patients and those retrieved from the GenBank database had amino acid changes at position 36 (V36L).
  
  
  CONCLUSIONS
  Our study suggests that the natural prevalence of strains resistant to HCV PIs does not differ between HCV-monoinfected and HIV/HCV-coinfected patients. Further studies on larger cohorts are needed to confirm these findings and to evaluate the impact of these mutations in clinical practice.
authors.affiliation: Virology Laboratory, Bordeaux University Hospital, France. pascale.trimoulet@chu-bordeaux.fr
authors.forename: P
authors.initials: P
authors.lastname: Trimoulet
authors.forename: C
authors.initials: C
authors.lastname: Belzunce
authors.forename: M
authors.initials: M
authors.lastname: Faure
authors.forename: L
authors.initials: L
authors.lastname: Wittkop
authors.forename: S
authors.initials: S
authors.lastname: Reigadas
authors.forename: M
authors.initials: M
authors.lastname: Dupon
authors.forename: J-M
authors.initials: JM
authors.lastname: Ragnaud
authors.forename: H
authors.initials: H
authors.lastname: Fleury
authors.forename: D
authors.initials: D
authors.lastname: Neau
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D060085:Coinfection; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics; D011480:Protease Inhibitors / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D010447:Peptide Hydrolases; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases