title: A boceprevir failure in a patient infected with HCV genotype 1g: importance and limitations of virus genotyping prior to HCV protease-inhibitor-based therapy.
abstract: A patient classified as HCV-1a-positive by both LiPA Siemens 2.0 and Abbott RealTime HCV Genotype II was instead found to be infected with HCV-1g, as determined by phylogenetic analysis of NS3 sequences. HCV-1g NS3 sequences available to date naturally harbour the resistance substitution T54S, plus P131S and L135F changes, located in the highly conserved NS3 positions within the boceprevir-binding site, as determined by structural modelling. HCV-1g NS3 sequences show some similarities to HCV-4 and are poorly responsive to interferon/ribavirin and to boceprevir/telaprevir; this patient was also a null-responder to boceprevir treatment. Baseline genotypic resistance testing may provide crucial information for the management of first-generation protease-inhibitor-based regimens, including both HCV genotype/subtype and natural resistance.
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: Valeria
authors: V
authors: Cento
authors: Simona
authors: S
authors: Landonio
authors: Francesca
authors: F
authors: De Luca
authors: Velia C
authors: VC
authors: Di Maio
authors: Valeria
authors: V
authors: Micheli
authors: Carmen
authors: C
authors: Mirabelli
authors: Fosca
authors: F
authors: Niero
authors: Carlo
authors: C
authors: Magni
authors: Giuliano
authors: G
authors: Rizzardini
authors: Carlo F
authors: CF
authors: Perno
authors: Francesca
authors: F
authors: Ceccherini-Silberstein
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D060005:Genotyping Techniques; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D017361:Viral Nonstructural Proteins / Q000145:classification / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D011392:Proline; 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; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide