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Original article

Patients with HCV genotype-1 who have failed a direct-acting antiviral regimen: virological characteristics and efficacy of retreatment

Mariantonietta Pisaturo, Mario Starace, Carmine Minichini, Stefania De Pascalis, Margherita Macera, Laura Occhiello, Vincenzo Messina, Vincenzo Sangiovanni, Ernesto Claar, Davide Precone, Gianfranca Stornaiuolo, Maria Stanzione, Ivan Gentile, Giuseppina Brancaccio, Salvatore Martini, Addolorata Masiello, Angelo Salomone Megna, Carmine Coppola, Alessandro Federico, Evangelista Sagnelli, Marcello Persico, Alfonso Galeota Lanza, Aldo Marrone, Giovanni Battista Gaeta, Nicola Coppola

Corresponding author name: Nicola Coppola
Corresponding author e-mail: nicola.coppola@unicampania.it

doi: 10.3851/IMP3296

Abstract

Background: This real-world clinical-setting study characterized the virological patterns in genotype-1 patients failing IFN-free regimens and evaluated the efficacy of re-treatment.

Methods: Seventy-three consecutive patients failing IFN-free regimens were enrolled (17 genotype 1a and 56 1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols.

Results: In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype 1a than in the 24 with genotype 1b (80% vs. 41.6%). In patients treated with an NS5A inhibitor, the prevalence of NS5A-RASs was very high in the 14 with genotype 1a and the 27 with genotype 1b (78.6% and 92.5%, respectively). In patients having failed sofosbuvir, the prevalence of NS5B-RASs was more frequently identified in the 45 with genotype 1b than in the 10 with genotype 1a (37.7% vs. 10%). The prevalence of NS5B-RASs in patients having failed dasabuvir was high in both genotypes, 66.6% in the 6 with genotype 1a and 45.5% in the 11 with genotype 1b.
The 6 patients re-treated with genotype 1a less frequently (50%) showed SVR than the 18 with genotype 1b (88.8%; p=0.07). SVR was more frequent in the 21 patients with an effective second-line DAA regimen than the 3 without (90.4% vs. 0%, p<0.005).

Conclusions: The prevalence of RASs was high in our real-world population. NS3, NS5A and NS5B sequencing seems mandatory in the choice of DAA re-treatment.

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