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Abstract Details
Virological patterns of hepatitis C virus patients with failure to the current-generation direct-acting antivirals
Int J Antimicrob Agents. 2020 Jun 26;106067. doi: 10.1016/j.ijantimicag.2020.106067.Online ahead of print.
M Pisaturo1, M Starace1, C Minichini1, S De Pascalis2, L Occhiello1, A Di Fraia1, V Messina3, V Sangiovanni4, E Claar5, N Coppola6, CampC Network
Author information
1Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania 'L. Vanvitelli', Napoli, Italy.
2Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania 'L. Vanvitelli', Napoli, Italy.
3Infectious Diseases Unit, A.O. S Anna e S Sebastiano, Caserta, Italy.
4Third Infectious Diseases Unit, AORN dei Colli, P.O. Cotugno, Naples, Italy.
5Internal Medicine Unit, Evangelical Hospital Villa Betania, Naples, Italy.
6Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania 'L. Vanvitelli', Napoli, Italy; Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania 'L. Vanvitelli', Napoli, Italy. Electronic address: nicola.coppola@unicampania.it.
Abstract
There are few data on the virological characterisation of patients with failure to current-generation direct-acting antivirals (DAAs), namely elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir. This study aimed to characterise virological patterns in patients with failure to current DAA regimens as well as the efficacy of re-treatment. All 61 consecutive hepatitis C virus (HCV) treatment-naïve patients with failure to current DAAs from January 2018 to February 2019 were enrolled. Sanger sequencing of NS3, NS5A and NS5B proteins was performed using homemade protocols. NS5A resistance-associated substitutions (RASs) were more frequent in the 17 patients treated with sofosbuvir/velpatasvir (89.5%) and 33 patients treated with elbasvir/grazoprevir (97%) compared with the 11 patients treated with glecaprevir/pibrentasvir (18.2%) (P = 0.002 and 0.000, respectively). NS3 RASs were more often detected in the 33 patients with failure to elbasvir/grazoprevir (30.3%) than in the 11 patients treated with glecaprevir/pibrentasvir (9.1%). NS3 RASs were also detected in 12% of sofosbuvir/velpatasvir-treated patients. NS5B RASs were infrequently identified. Of the glecaprevir/pibrentasvir-treated patients, 73% did not show RASs in any HCV regions, a prevalence higher than that observed in those treated with elbasvir/grazoprevir (0%; P < 0.05) or sofosbuvir/velpatasvir (12%; P < 0.05). Of the 61 patients, 21 (34.4%) were re-treated with sofosbuvir/velpatasvir and voxilaprevir. All patients achieved sustained virological response at 12 weeks (SVR12). To our knowledge, this is one of the first real-life studies describing patients who failed current-generation DAAs; the prevalence of RASs differed according to the DAA regimen used, and the efficacy of re-treatment was high.