The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Prevalence of resistance-associated substitutions to NS3, NS5A and NS5B inhibitors at DAA-failure in hepatitis C virus in Italy from 2015 to 2019
Infez Med. 2021 Jun 1;29(2):242-251.
Barbara Rossetti1, Lorenzo Paglicci2, Velia C Di Maio3, Chiara Cassol2, Silvia Barbaliscia3, Stefania Paolucci4, Bianca Bruzzone5, Nicola Coppola6, Francesca Montagnani2, Valeria Micheli7, Laura Monno8, Giacomo Zanelli2, Teresa Santantonio9, Nunzia Cuomo10, Cinzia Caudai11, Maurizio Zazzi12, Francesca Ceccherini-Silberstein3, C On Behalf Of The Hcv Virology Italian Resistance Network Vironet
1Department of Specialized and Internal Medicine, Tropical and Infectious Diseases Unit, University Hospital of Siena, Siena, Italy.
2Department of Specialized and Internal Medicine, Tropical and Infectious Diseases Unit, University Hospital of Siena, Siena, Italy; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
3Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
4Molecular Virology Unit, Microbiology and Virology Department, IRCCS Polyclinic Foundation San Matteo, Pavia, Italy.
5Hygiene Unit, IRCCS AOU San Martino-IST, Genoa, Italy.
6Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania "L. Vanvitelli", Naples, Italy.
7Clinical Microbiology, Virology and Bioemergencies, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy.
8Infectious Diseases Unit, University of Bari, Bari, Italy.
9Infectious Diseases Unit, University of Foggia, Foggia, Italy.
10Microbiology and Virology Unit, Azienda Ospedaliera Specialistica dei Colli Monaldi - Cotugno - C.T.O., Naples, Italy.
11Microbiology and Virology Unit, AOU Senese, Siena, Italy.
12Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Despite the high efficacy of direct-acting antivirals (DAAs), the selection of resistance-associated substitutions (RASs) after virological failure of hepatitis C virus (HCV) DAAs can impair the cure of chronic HCV. The aim of the study was to characterize RASs after virological failure of DAAs in Italy over the years. Within the Italian network VIRONET-C, the change in prevalence of NS3/4A-NS5A-NS5B RASs was retrospectively evaluated in patients who failed a DAA regimen over the years 2015-2019. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols and the geno2pheno system was used to define HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend. Predictors of RASs at failure were analysed by logistic regression. Among 468 HCV-infected patients, HCV genotype 1 was the most prevalent (1b in 154, 33% and 1a in 109, 23%). DAA regimens were: ledipasvir (LDV)/sofosbuvir (SOF) in 131 patients (28%), daclatasvir (DCV)/SOF in 109 (23%), ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) in 89 (19%), elbasvir (EBR)/grazoprevir (GRZ) in 52 (10.5%), velpatasvir (VEL)/SOF in 53 (11%), glecaprevir (GLE)/pibrentasvir (PIB) in 27 (6%) and ombitasvir/paritaprevir/ritonavir (2D) in 7 (1.5%); ribavirin was administered in 133 (28%). The NS5A fasta sequence was available for all patients, NS5B and NS3/4A both for 93%. The prevalence of NS5A and NS3/4A RASs significantly declined from 2015 to 2019; NS5B RAS remained stable. Independent predictors of any RASs included older age and genotype 1a (vs G2 and vs G4). Notably, at least partial susceptibility to all the agents included in the GLE/PIB and VEL/SOF/Voxilaprevir (VOX) combinations was predicted in >95% of cases. As RASs remain common at the failure of DAAs, their identification could play a crucial role in optimizing re-treatment strategies. In Italy RAS prevalence has been decreasing over the years and susceptibility to the latest developed drug combinations is maintained in most cases.