Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C

Vincenza Calvaruso, Vito Di Marco, Antonio Craxi, Alessio Aghemo, Ana Lleo, Ilaria Lenci, Enzo Boeri, Vincenzo Sangiovanni, Andreone, Vincenza Calvaruso, Ennio Polilli, Valeria Cento, Maurizia Rossana Brunetto, Mario Angelico, Di Stefano, Simona Marenco, Giovanni Battista Gaeta, Alessandro Pieri, Chiara Masetti, Elisabetta TetiMartina Milana, Velia Chiara Di Maio, Mario Starace, Minichini, Francesca Ceccherini-Silberstein, Giovanni Di Perri, Tina Ruggiero, Giustino Parruti, Marianna Aragri, Silvia Barbaliscia, Giovanni Raimondo, Giulia Morsica, Milano, Ada Bertoli, Bianca Bruzzone, Teresa Santantonio, Luca Foroghi, Di Biagio, Miriam Lichtner, Claudio Mastroianni, Sergio Babudieri, Giuseppina Brancaccio, Ivana Maida, Toniutto, Barbara Rossetti, Monno, Katia Yu La Rosa, Puoti, Carlo Federico Perno, Gianluca Fiorentino, Paternoster, William Gennari, Giovanni Cenderello, Cuomo, Antonio Ciaccio, Annapaola Callegaro, Pace Palitti, Roberto Gulminetti, Caterina Pasquazzi, Stefano Novati, Simona Landonio, Teresa Pollicino, Nicola Coppola, Alessia Ciancio, Valeria Ghisetti, Adriano Pellicelli, Loredana Sarmati, Rizzardini, Maurizio Zazzi, Valeria Micheli, Fausto Baldanti, Vito Di Marco, Vullo, Stefania Paolucci, Massimo Andreoni, Antonio Craxì, Gloria Taliani, Pietro Lampertico, De Santis

Risultato della ricerca: Articlepeer review

Abstract

Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P <.001) followed by A30K (12.7% vs 2.8% in DAA-naïve, P <.001). Analysing baseline samples, a higher prevalence of NS5A-RASs was observed before treatment in DAA-failures (5/13, 38.5%) vs DAA-naïves (61/393, 15.5%, P =.04). Regarding 228 DAA-naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A-RASs (P =.002). Conclusions: In this real-life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A-RASs, the most frequent being Y93H. The presence of natural NS5A-RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens.
Lingua originaleEnglish
pagine (da-a)1802-1814
Numero di pagine13
RivistaLiver International
Volume41
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

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