title: Multicenter quality control of hepatitis C virus protease inhibitor resistance genotyping.
abstract: Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.
authors: Université de Brest, UFR Médecine et des Sciences de la Santé, LUBEM, Brest, France. sophie.vallet@chu-brest.fr
authors: Sophie
authors: S
authors: Vallet
authors: Sylvie
authors: S
authors: Larrat
authors: Syria
authors: S
authors: Laperche
authors: Hélène
authors: H
authors: Le Guillou-Guillemette
authors: Florence
authors: F
authors: Legrand-Abravanel
authors: Françoise
authors: F
authors: Bouchardeau
authors: Adeline
authors: A
authors: Pivert
authors: Cécile
authors: C
authors: Henquell
authors: Audrey
authors: A
authors: Mirand
authors: Elisabeth
authors: E
authors: André-Garnier
authors: Valérie
authors: V
authors: Giordanengo
authors: Gisèle
authors: G
authors: Lagathu
authors: Vincent
authors: V
authors: Thibault
authors: Caroline
authors: C
authors: Scholtes
authors: Evelyne
authors: E
authors: Schvoerer
authors: Catherine
authors: C
authors: Gaudy-Graffin
authors: Sarah
authors: S
authors: Maylin
authors: Pascale
authors: P
authors: Trimoulet
authors: Etienne
authors: E
authors: Brochot
authors: Sébastien
authors: S
authors: Hantz
authors: Joël
authors: J
authors: Gozlan
authors: Anne-Marie
authors: AM
authors: Roque-Afonso
authors: Patrick
authors: P
authors: Soussan
authors: Jean-Christophe
authors: JC
authors: Plantier
authors: Charlotte
authors: C
authors: Charpentier
authors: Stéphane
authors: S
authors: Chevaliez
authors: Philippe
authors: P
authors: Colson
authors: Vincent
authors: V
authors: Mackiewicz
authors: Lina
authors: L
authors: Aguilera
authors: Sylvain
authors: S
authors: Rosec
authors: Stéphanie
authors: S
authors: Gouriou
authors: Nelly
authors: N
authors: Magnat
authors: Françoise
authors: F
authors: Lunel-Fabiani
authors: Jacques
authors: J
authors: Izopet
authors: Patrice
authors: P
authors: Morand
authors: Christopher
authors: C
authors: Payan
authors: Jean-Michel
authors: JM
authors: Pawlotsky
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011786:Quality Control; 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; 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