Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2-45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4-19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1-4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.
Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy / Bertoli, Ada; Sorbo, Maria Chiara; Aragri, Marianna; Lenci, Ilaria; Teti, Elisabetta; Polilli, Ennio; Di Maio, Velia Chiara; Gianserra, Laura; Biliotti, Elisa; Masetti, Chiara; Magni, Carlo F.; Babudieri, Sergio; Nicolini, Laura A.; Milana, Martina; Cacciatore, Pierluigi; Sarmati, Loredana; Pellicelli, Adriano; Paolucci, Stefania; Craxì, Antonio; Morisco, Filomena; Palitti, Valeria Pace; Siciliano, Massimo; Coppola, Nicola; Iapadre, Nerio; Puoti, Massimo; Rizzardini, Giuliano; Taliani, Gloria; Pasquazzi, Caterina; Andreoni, Massimo; Parruti, Giustino; Angelico, Mario; Perno, Carlo Federico; Cento, Valeria; Ceccherini-Silberstein, Francesca; Andreone, Pietro; Baldanti, Fausto; Barbarini, Giorgio; Boccaccio, Vincenzo; Boglione, Lucio; Bolis, Matteo; Bonora, Stefano; Borghi, Vanni; Brancaccio, Giuseppina; Bruno, Savino; Bruzzone, Bianca; Calvaruso, Vincenza; Caporaso, Nicola; Ciaccio, Antonio; Ciancio, Alessia; Colombatto, Piero; Cozzolongo, Raffaele; D'Ambrosio, Cecilia; D'Ettorre, Gabriella; De Leonardis, Francesco; De Luca, Andrea; Di Biagio, Antonio; Di Perri, Giovanni; Francioso, Simona; Gaeta, Giovanni Battista; Gasbarrini, Antonio; Ghisetti, Valeria; Giorgini, Alessia; Grieco, Antonio; Gubertini, Guido; Gulminetti, Roberto; Lambiase, Lara; Landonio, Simona; Lichtner, Miriam; Maida, Ivana; Marenco, Simona; Marinaro, Letizia; Maserati, Renato; Melis, Michela; Menzaghi, Barbara; Meregalli, Elisa; Micheli, Valeria; Niero, Fosca; Paoloni, Maurizio; Pieri, Alessandro; Rendina, Maria; Romagnoli, Dante; Rossetti, Barbara; Ruggiero, Tina; Sangiovanni, Vincenzo; Starace, Mario; Sticchi, Laura; Tarquini, Pierluigi; Toniutto, Pierluigi; Vullo, Vincenzo; Zazzi, Maurizio. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 8:1(2018), pp. 1-11. [10.1038/s41598-018-26862-y]
Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy
Andreone, Pietro;
2018
Abstract
Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2-45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4-19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1-4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.
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