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 regimen
Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C / 1, Velia Chiara Di Maio; 1, Silvia Barbaliscia; 2, Elisabetta Teti; 3, Gianluca Fiorentino; 4, Martina Milana; 5, Stefania Paolucci; 6, Teresa Pollicino; 7, Giulia Morsica; 8, Mario Starace; 9, Bianca Bruzzone; Gennari 10, William; Micheli 11, Valeria; 1, Katia Yu La Rosa; 2, Luca Foroghi; Calvaruso 12, Vincenza; 4, Ilaria Lenci; Polilli 13, Ennio; Babudieri, Sergio; Aghemo 15, Alessio; 6, Giovanni Raimondo; 2, Loredana Sarmati; 8 16, Nicola Coppola; 3, Caterina Pasquazzi; 5, Fausto Baldanti; Parruti 13, Giustino; Federico Perno 17, Carlo; 4, Mario Angelico; Craxì 12, Antonio; 2, Massimo Andreoni; P Andreone, Francesca Ceccherini-Silberstein; Aragri, M; Bertoli, A; Boeri, E; Brancaccio, G; Brunetto, M; P Callegaro, A; Cenderello, G; Cento, V; Ciaccio, A; Ciancio, A; Cuomo, N; De Santis, A; Di Biagio, A; Di Marco, V; Di Perri, G; A Di Stefano, M; B Gaeta, G; Ghisetti, V; Gulminetti, R; Lampertico, P; Landonio, S; Lichtner, M; Lleo, A; Maida, I; Marenco, S; Masetti, C; Mastroianni, C; Minichini, C; Milano, E; Monno, L; Novati, S; Pace Palitti, V; Paternoster, C; Pellicelli, A; Pieri, A; Puoti, M; Rizzardini, G; Ruggiero, T; Rossetti, B; Sangiovanni, V; Santantonio, T; Taliani, G; Toniutto, P; Vullo, V; Zazzi, M. - In: LIVER INTERNATIONAL. - ISSN 1478-3223. - (2021). [10.1111/liv.14797]
Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C
Sergio Babudieri;I Maida;
2021-01-01
Abstract
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 regimenI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
