title: Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype-1 patients with or without HIV coinfection.
abstract: BACKGROUND
  HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients.
  
  
  METHODS
  We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology.
  
  
  RESULTS
  HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations.
  
  
  CONCLUSIONS
  Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample.
authors.affiliation: Department of Infectious Diseases, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
authors.forename: Gaspar
authors.initials: G
authors.lastname: Lisboa-Neto
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Noble
authors.forename: João R Rebello
authors.initials: JR
authors.lastname: Pinho
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Malta
authors.forename: Michele S
authors.initials: MS
authors.lastname: Gomes-Gouvêa
authors.forename: Mónica V
authors.initials: MV
authors.lastname: Alvarado-Mora
authors.forename: Mariliza H
authors.initials: MH
authors.lastname: da Silva
authors.forename: Andrea G B
authors.initials: AG
authors.lastname: Leite
authors.forename: Leonora Z
authors.initials: LZ
authors.lastname: Piccoli
authors.forename: Flaviane K
authors.initials: FK
authors.lastname: Rodrigues
authors.forename: Flair J
authors.initials: FJ
authors.lastname: Carrilho
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mendes-Correa
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001938:Brazil; D060085:Coinfection; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011480:Protease Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; 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; 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