Since RASs are commonly detected at failure of interferonfree direct-acting-antiviral (DAA) regimens,2–6 we were interested in characterizing NS3, NS5A and NS5B RASs across different HCV-genotypes/subtypes by analysing patients infected with HCV, who failed a recommended DAA-regimen in an Italian real-life setting. Despite the excellent efficacy of DAAs, some patients still fail to eradicate HCV, and the characterization of the resistance profile can be helpful to guide retreatment choices for all HCV genotypes/subtypes. Within the Italian network VIRONET-C, out of a total of 569 interferon-free DAA failing-patients, 468 had a valid genotypic-resistance-test (GRT) at failure. Of these, 310 failed (from 2015 to 2017) an interferon-free DAA-regimen recommended by 2016–2017 European guidelines4 and available in Italy, namely: simeprevir + sofosbuvir ± ribavirin (n = 84), daclatasvir/ledipasvir + sofosbuvir ± ribavirin (n = 58/91), 3D/2D (paritaprevir/ombitasvir + dasabuvir) ± ribavirin (n = 47/2), sofosbuvir + ribavirin (genotype 2, n = 28). All 310 patients had a NS3-protease and/or NS5A and/or NS5B GRT performed by Sanger-sequencing at virological-failure, using validated home-made protocols at 10 Italian centers. In addition, 48 patients also had a baseline GRT. Available sequences were used to determine HCV genotype/subtype through phylogenetic analysis. A RAS reference list was generated according to published manuscripts.
Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens? / Di Maio, Vc; Cento, V; Aragri, M; Paolucci, S; Pollicino, T; Coppola, N; Bruzzone, B; Ghisetti, V; Zazzi, M; Brunetto, M; Bertoli, A; Barbaliscia, S; Galli, S; Gennari, W; Baldanti, F; Raimondo, G; Perno, Cf; Ceccherini-Silberstein, Francesca; Andreone, P; Andreoni, M; Angelico, M; Babudieri, S; Barbarini, G; Boccaccio, V; Boglione, L; Bolis, M; Bonora, S; Borghi, V; Brancaccio, G; Bruno, S; Cacciatore, P; Calvaruso, V; Caporaso, N; Ciaccio, A; Ciancio, A; Colombatto, P; Cozzolongo, R; Craxì, A; D'Ambrosio, C; D'Ettorre, G; De Luca, A; Di Biagio, A; Di Perri, G; Francioso, S; Gaeta, Gb; Giorgini, A; Grieco, A; Gubertini, G; Gulminetti, R; Lambiase, L; Lenci, I; Lichtner, M; Maida, I; Marenco, S; Marinaro, L; Maserati, R; Masetti, C; Melis, M; Meregalli, E; Micheli, V; Morisco, F; Niero, F; Nicolini, La; Palitti, Vp; Paoloni, M; Parruti, G; Pasquazzi, C; Pellicelli, A; Polilli, E; Ponti, Ml; Puoti, M; Rendina, M; Rizzardini, G; Rossetti, B; Ruggiero, T; Sangiovanni, V; Starace, M; Sticchi, L; Tarquini, P; Toniutto, P; Vullo, V.. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 68:3(2018), pp. 597-600. [10.1016/j.jhep.2017.09.008]
Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?
Babudieri, S;Maida, I;Melis, M;
2018-01-01
Abstract
Since RASs are commonly detected at failure of interferonfree direct-acting-antiviral (DAA) regimens,2–6 we were interested in characterizing NS3, NS5A and NS5B RASs across different HCV-genotypes/subtypes by analysing patients infected with HCV, who failed a recommended DAA-regimen in an Italian real-life setting. Despite the excellent efficacy of DAAs, some patients still fail to eradicate HCV, and the characterization of the resistance profile can be helpful to guide retreatment choices for all HCV genotypes/subtypes. Within the Italian network VIRONET-C, out of a total of 569 interferon-free DAA failing-patients, 468 had a valid genotypic-resistance-test (GRT) at failure. Of these, 310 failed (from 2015 to 2017) an interferon-free DAA-regimen recommended by 2016–2017 European guidelines4 and available in Italy, namely: simeprevir + sofosbuvir ± ribavirin (n = 84), daclatasvir/ledipasvir + sofosbuvir ± ribavirin (n = 58/91), 3D/2D (paritaprevir/ombitasvir + dasabuvir) ± ribavirin (n = 47/2), sofosbuvir + ribavirin (genotype 2, n = 28). All 310 patients had a NS3-protease and/or NS5A and/or NS5B GRT performed by Sanger-sequencing at virological-failure, using validated home-made protocols at 10 Italian centers. In addition, 48 patients also had a baseline GRT. Available sequences were used to determine HCV genotype/subtype through phylogenetic analysis. A RAS reference list was generated according to published manuscripts.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
