title: Predominance of hepatitis C virus Q80K among NS3 baseline-resistance-associated amino acid variants in direct-antiviral-agent-naïve patients with chronic hepatitis: single-centre experience.
abstract: In the era of direct-acting antiviral agents (DAAs), hepatitis C virus (HCV) genotyping tests at baseline are controversial. The HCV NS3-Q80K polymorphism is associated with resistance to the recently approved NS3 inhibitor simeprevir (SMV) when combined with PEG-interferon and ribavirin (PEG-IFN/RBV) and alternative therapy should be considered for patients with baseline Q80K. The aim of this study was to provide an estimate of Q80K prevalence at baseline in a study group of 205 DAA-naïve patients (21% of them with HIV coinfection) using NS3 full-population direct sequencing to detect resistance-associated amino acid variants (RAVs). NS3 RAVs were identified in 56 patients (27.3%). Q80K was the most frequently reported one (41%), in both HIV/HCV-coinfected and HCV-monoinfected patients, but it was only detectable in cases of HCV-subtype 1a infection. Therefore, in clinical practice, an NS3-Q80K genotyping test prior to simeprevir plus PEG-IFN/RBV treatment is highly recommended.
authors.affiliation: Laboratory of Microbiology and Virology, Department of Infectious Diseases, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149, Turin, Italy. tinarugg@gmail.com.
authors.forename: Tina
authors.initials: T
authors.lastname: Ruggiero
authors.affiliation: Laboratory of Microbiology and Virology, Department of Infectious Diseases, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149, Turin, Italy.
authors.forename: Alex
authors.initials: A
authors.lastname: Proietti
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, C.so Svizzera 164, 10149, Turin, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Boglione
authors.affiliation: Laboratory of Microbiology and Virology, Department of Infectious Diseases, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149, Turin, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Milia
authors.affiliation: Laboratory of Microbiology and Virology, Department of Infectious Diseases, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149, Turin, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Allice
authors.affiliation: Laboratory of Microbiology and Virology, Department of Infectious Diseases, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149, Turin, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Burdino
authors.affiliation: Unit A of Infectious Diseases, Department of Infectious Diseases, Amedeo di Savoia Hospital, C.so Svizzera 164, 10149, Turin, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Orofino
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, C.so Svizzera 164, 10149, Turin, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, C.so Svizzera 164, 10149, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Laboratory of Microbiology and Virology, Department of Infectious Diseases, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149, Turin, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ghisetti
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D000069616:Simeprevir / Q000627:therapeutic use*; 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