title: Naturally occurring hepatitis C virus (HCV) NS3/4A protease inhibitor resistance-related mutations in HCV genotype 1-infected subjects in Italy.
abstract: OBJECTIVE
  To assess the prevalence of hepatitis C virus (HCV) NS3/4A protease inhibitor (PI) resistance mutations in HCV genotype 1-infected PI-naive individuals in Italy.
  
  
  METHODS
  One hundred and twelve patients infected with HCV genotype 1a or 1b (based on Versant HCV Genotype 2.0 or 5'UTR/core sequencing) and never treated with any HCV PI were evaluated. The whole NS3 region was analysed by population sequencing and mutations related to resistance to linear and macrocyclic PIs were recorded.
  
  
  RESULTS
  Forty-six HCV-monoinfected and 66 HCV/HIV-coinfected subjects were studied. Complete NS3 sequence information was obtained for 109 (97.3%) samples: 67 subtype 1a and 42 subtype 1b. Subtype assignment by NS3 sequencing was concordant in 100.0% and 83.9% of cases with the original 5'UTR sequencing and Versant result, respectively. At least one mutation related to PI resistance was detected in 21 (19.3%) isolates. However, 11 of these had only Q80K, expected to confer resistance to one investigational macrocyclic compound, and were detected only in subtype 1a. Boceprevir and telaprevir resistance-related mutations were detected in 10 (9.2%) isolates and included V36L, T54S and V55A. Only one isolate harboured two mutations (V36L and T54S). There was no association between HCV PI resistance and HIV coinfection or exposure to HIV PIs.
  
  
  CONCLUSIONS
  A minority of untreated HCV genotype 1 patients in Italy harbour a virus population carrying HCV PI resistance-related mutations. The clinical implications of this finding warrant further analysis.
authors.affiliation: Department of Biotechnology,  University of Siena, Siena,  Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Vicenti
authors.forename: Andrea
authors.initials: A
authors.lastname: Rosi
authors.forename: Francesco
authors.initials: F
authors.lastname: Saladini
authors.forename: Genny
authors.initials: G
authors.lastname: Meini
authors.forename: Francesco
authors.initials: F
authors.lastname: Pippi
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossetti
authors.forename: Letizia
authors.initials: L
authors.lastname: Sidella
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Paolo
authors.initials: P
authors.lastname: Almi
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Cinzia
authors.initials: C
authors.lastname: Caudai
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D024882:Drug Resistance, Viral; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007558:Italy / Q000453:epidemiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D015995:Prevalence; D011480:Protease Inhibitors / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; 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; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011480:Protease Inhibitors; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus