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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels
Journal of Antimicrobial Chemotherapy, Volume 71, No. 3, Year 2016
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Description
Objectives: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. Methods: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. Results: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA > 3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤ 3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). Conclusions: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: A correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Di Maio, Velia Chiara
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Cento, Valeria
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Di Paolo, Daniele
Italy, Rome
Policlinico Tor Vergata
Aragri, Marianna
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Micheli, Valeria
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Bellocchi, Maria Concetta
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Antonucci, Francescopaolo
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Bertoli, A.
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Lenci, Ilaria
Italy, Rome
Policlinico Tor Vergata
Gianserra, Laura
Italy, Rome
Sapienza Università Di Roma
Melis, Michela
Italy, Sassari
Università Degli Studi Di Sassari
Di Biagio, Antonio
Italy, Genoa
Università Degli Studi Di Genova
Sarmati, Loredana
Italy, Rome
Policlinico Tor Vergata
Landonio, Simona
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Francioso, Simona
Italy, Rome
Policlinico Tor Vergata
Nicolini, Laura Ambra
Italy, Genoa
Università Degli Studi Di Genova
Marenco, Simona
Italy, Genoa
Università Degli Studi Di Genova
Siciliano, Massimo
Italy, Rome
Università Cattolica Del Sacro Cuore, Campus Di Roma
Romagnoli, Dante
Unknown Affiliation
Pellicelli, A. M.
Italy, Rome
Azienda Ospedaliera San Camillo Forlanini
Magni, Carlo Federico
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Babudieri, Sergio
Italy, Sassari
Università Degli Studi Di Sassari
Taliani, Gloria L.
Italy, Rome
Azienda Ospedaliera Universitaria Policlinico Umberto I
Mastroianni, Claudio Maria
Italy, Rome
Sapienza Università Di Roma
Morisco, Filomena
Italy, Naples
Università Degli Studi Di Napoli Federico Ii
Vullo, Vincenzo
Italy, Rome
Sapienza Università Di Roma
Bruno, Serena Rita
Italy, Pieve Emanuele
Humanitas University
Pasquazzi, Caterina
Italy, Rome
Sapienza Università Di Roma
Tisone, Giuseppe
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Picciotto, Antonino
Italy, Genoa
Università Degli Studi Di Genova
Andreoni, Massimo G.
Italy, Rome
Policlinico Tor Vergata
Parruti, Giustino
Italy, Pescara
Pescara General Hospital
Rizzardini, Giuliano
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Angelico, Mario
Italy, Rome
Policlinico Tor Vergata
Perno, Carlo Federico
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Italy, Rome
Policlinico Tor Vergata
Ceccherini-Silberstein, Francesca
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Mariani, Rinalda
Unknown Affiliation
Paoloni, Maurizio
Unknown Affiliation
Iapadre, Nerio
Unknown Affiliation
Grimaldi, Alessandro
Unknown Affiliation
Menzaghi, Barbara
Unknown Affiliation
Quirino, Tiziana
Unknown Affiliation
Bruzzone, Bianca Marisa
Unknown Affiliation
de Maria, Andrea F.
Unknown Affiliation
Viscoli, Claudio
Unknown Affiliation
Casinelli, Katia
Unknown Affiliation
Delle Monache, Marco
Unknown Affiliation
Lichtner, Miriam
Unknown Affiliation
Aghemo, Alessio
Unknown Affiliation
Colombo, Massimo Giuseppe
Unknown Affiliation
D'Arminio Monforte, Antonella D.
Unknown Affiliation
Danieli, Elena
Unknown Affiliation
Donato, Maria Francesca
Unknown Affiliation
Gubertini, Guido A.
Unknown Affiliation
Mancon, Alessandro
Unknown Affiliation
Monico, Sara
Unknown Affiliation
Niero, Fosca P.
Unknown Affiliation
Puoti, Massimo
Unknown Affiliation
Russo, Monia L.
Unknown Affiliation
Alfieri, R.
Unknown Affiliation
Gnocchi, Matteo
Unknown Affiliation
Orro, Alessandro
Unknown Affiliation
Milanesi, Luciano
Unknown Affiliation
Baldelli, Enrica
Unknown Affiliation
Bertolotti, Marco
Unknown Affiliation
Borghi, Vanni
Unknown Affiliation
Mussini, Cristina
Unknown Affiliation
Brancaccio, Giuseppina
Unknown Affiliation
Caporaso, Nicola
Unknown Affiliation
Gaeta, Giovanni Battista
Unknown Affiliation
Lembo, Vincenzo
Unknown Affiliation
Calvaruso, Vincenza
Unknown Affiliation
Craxì, Antonio
Unknown Affiliation
Di Marco, Vito
Unknown Affiliation
Mazzola, Alessandra
Unknown Affiliation
Petta, Salvatore
Unknown Affiliation
D'Amico, Emilio
Unknown Affiliation
Cacciatore, Pierluigi
Unknown Affiliation
Consorte, Augusta
Unknown Affiliation
Pace-Palitti, Valeria
Unknown Affiliation
Pieri, Alessandro
Unknown Affiliation
Polilli, Ennio
Unknown Affiliation
Antenucci, F.
Unknown Affiliation
Armenia, D.
Unknown Affiliation
Baiocchi, Lorenzo
Unknown Affiliation
Biliotti, Elisa
Unknown Affiliation
Biolato, Marco
Unknown Affiliation
Carioti, Luca
Unknown Affiliation
Cerva, Carlotta
Unknown Affiliation
Ciotti, Marco
Unknown Affiliation
D'Ettorre, Gabriella
Unknown Affiliation
Grieco, Antonio
Unknown Affiliation
Malagnino, Vincenzo
Unknown Affiliation
Merli, Manuela
Unknown Affiliation
Santopaolo, Francesco
Unknown Affiliation
Santoro, Maria Mercedes
Unknown Affiliation
Svicher, Valentina
Unknown Affiliation
Teti, Elisabetta
Unknown Affiliation
Mangia, A.
Unknown Affiliation
Tarquini, Pierluigi L.
Unknown Affiliation
Statistics
Citations: 13
Authors: 100
Affiliations: 16
Identifiers
Doi:
10.1093/jac/dkv403
ISSN:
03057453
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study