title: Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection.
abstract: Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection.
  
  
  METHODS
  HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients.
  
  
  RESULTS
  148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses.
  
  
  CONCLUSIONS
  In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.
authors: † Department of Gastroenterology and Hepatology University Medical Center Utrecht, Utrecht, the Netherlands; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Faydra I
authors: FI
authors: Lieveld
authors: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Niels
authors: N
authors: Swaans
authors: Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, Amsterdam, The Netherlands.
authors: Astrid M
authors: AM
authors: Newsum
authors: Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Cynthia K Y
authors: CK
authors: Ho
authors: Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Janke
authors: J
authors: Schinkel
authors: Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Richard
authors: R
authors: Molenkamp
authors: ¶ Department of Internal Medicine and Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors: Jan T M
authors: JT
authors: van der Meer
authors: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Joop E
authors: JE
authors: Arends
authors: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Andy I M
authors: AI
authors: Hoepelman
authors: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Anne M J
authors: AM
authors: Wensing
authors: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: Peter D
authors: PD
authors: Siersema
authors: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Karel J
authors: KJ
authors: van Erpecum
authors: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Greet J
authors: GJ
authors: Boland
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D060085:Coinfection; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis / Q000453:epidemiology*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D055815:Young Adult; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases