title: Worldwide distribution of the NS3 gene 80K polymorphism among circulating hepatitis C genotype 1 viruses: implication for simeprevir usage.
abstract: OBJECTIVE
  Several direct-acting agents against the hepatitis C virus (HCV) NS3 protease and NS5b polymerase have been developed in recent years to improve treatment of this viral infection. Of these, simeprevir is currently recommended for HCV genotype 1 and 4 infections, but genotypic assessment for the presence of 80K is required prior to simeprevir administration due to the reduced susceptibility of genotype 1 viruses carrying that polymorphism. Because the prevalence of 80K at baseline in genotype 1 viruses varies between reports, we wanted to assess its worldwide prevalence.
  
  
  METHODS
  Over 3000 HCV genotype 1 sequences reported from drug-naive subjects distributed around the world were retrieved from the HCV Los Alamos and GenBank databases. These were categorized into subtypes and geographical provenance (continent and country), and the presence of the 80K and 80R polymorphisms was visually inspected and counted.
  
  
  RESULTS
  Disparate prevalence of 80K was observed depending on the country/continent analysed. While in resource-rich areas (USA, Western Europe and Australia) a high prevalence of 80K was seen in HCV subtype 1a, in emerging countries, such as Brazil, this prevalence was very low (<1%). HCV subtype 1b sequences from France also displayed a significant occurrence of 80K (6.1%). 80R, on the other hand, was negligible worldwide.
  
  
  CONCLUSIONS
  The genotypic assessment of 80K in HCV subtype 1a prior to simeprevir administration in emerging countries with significant numbers of HCV infection is questionable, while it should be performed for subtype 1b in certain developed countries.
authors.affiliation: Laboratório de Virologia Humana, Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luãnna L
authors.initials: LL
authors.lastname: Vidal
authors.affiliation: Laboratório de Virologia Humana, Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Santos
authors.affiliation: Laboratório de Virologia Humana, Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Programa de Oncovirologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil masoares@inca.gov.br.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Soares
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D014644:Genetic Variation; D005838:Genotype; D014943:Global Health; D016174:Hepacivirus / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D017720:Molecular Epidemiology; D058974:Phylogeography; D000069616:Simeprevir / Q000494:pharmacology*; 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; D000069616:Simeprevir; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: 80R; PIs; genotyping; protease inhibitors