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Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies
Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies
- Source :
- Liver international, 37 (2017): 514–528. doi:10.1111/liv.13327, info:cnr-pdr/source/autori:Di Maio, Velia C.; Cento, Valeria; Lenci, Ilaria; Aragri, Marianna; Rossi, Piera; Barbaliscia, Silvia; Melis, Michela; Verucchi, Gabriella; Magni, Carlo F.; Teti, Elisabetta; Bertoli, Ada; Antonucci, FrancescoPaolo; Bellocchi, Maria C.; Micheli, Valeria; Masetti, Chiara; Landonio, Simona; Francioso, Simona; Santopaolo, Francesco; Pellicelli, Adriano M.; Calvaruso, Vincenza; Gianserra, Laura; Siciliano, Massimo; Romagnoli, Dante; Cozzolongo, Raffaele; Grieco, Antonio; Vecchiet, Jacopo; Morisco, Filomena; Merli, Manuela; Brancaccio, Giuseppina; Di Biagio, Antonio; Loggi, Elisabetta; Mastroianni, Claudio M.; Palitti, Valeria Pace; Tarquini, Pierluigi; Puoti, Massimo; Taliani, Gloria; Sarmati, Loredana; Picciotto, Antonino; Vullo, Vincenzo; Caporaso, Nicola; Paoloni, Maurizio; Pasquazzi, Caterina; Rizzardini, Giuliano; Parruti, Giustino; Craxi, Antonio; Babudieri, Sergio; Andreoni, Massimo; Angelico, Mario; Perno, Carlo F.; Ceccherini-Silberstein, Francesca; Mariani R, Iapadre N, Grimaldi A, Cozzolongo R, Andreone P, Verucchi G, Menzaghi B, Quirino T, Pisani V, Torti C, Vecchiet J, Bruzzone B, De Maria A, Marenco S, Nicolini LA, Viscoli C, Casinelli K, Delle Monache M, Lichtner M, Aghemo A, Boccaccio V, Bruno S, Cerrone M, Colombo M, D'Arminio Monforte A, Danieli E, Donato F, Gubertini G, Lleo A, Magni CF, Mancon A, Monico S, Niero F, Russo ML, Gnocchi M, Orro A, Milanesi L, Baldelli E, Bertolotti M, Borghi V, Mussini C, Brancaccio G, Gaeta GB, Lembo V, Sangiovanni V, Di Marco V, Mazzola A, Petta S, D'Amico E, Cacciatore P, Consorte A, Pieri A, Polilli E, Sozio F, Antenucci F, Aragri M, Baiocchi L, Barbaliscia S, Biliotti E, Biolato M, Carioti L, Ceccherini-Silberstein F, Cerasari G, Cerva C, Ciotti M, D'Ambrosio C, D'Ettorre G, De Leonardis F, De Sanctis A, Di Maio VC, Di Paolo D, Furlan C, Gallo P, Gasbarrini A, Giannelli V, Grieco S, Lambiase L, Lattanzi B, Lenci I, Lula R, Malagnino V, Manuelli M, Miglioresi L, Milana M, Moretti A, Nosotti L, Palazzo D, Pellicelli A, Romano M, Sarrecchia C, Sforza D, Sorbo MC, Spaziante M, Svicher V, Tisone G, Vespasiani-Gentilucci U, D'Adamo G, Mangia A, Maida I, Mura MS, Falconi L, Di Giammartino D./titolo:Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies/doi:10.1111%2Fliv.13327/rivista:Liver international (Print)/anno:2017/pagina_da:514/pagina_a:528/intervallo_pagine:514–528/volume:37
- Publication Year :
- 2017
- Publisher :
- Blackwell Publishing Ltd, 2017.
-
Abstract
- Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.
- Subjects :
- Male
0301 basic medicine
hepatitis C virus
Sustained Virologic Response
Sofosbuvir
Hepacivirus
Drug Resistance
resistance-associated substitutions
Viral Nonstructural Proteins
VARIANTS
NS5A
medicine.disease_cause
Gastroenterology
chemistry.chemical_compound
0302 clinical medicine
Recurrence
INFECTION
antiviral therapy
Medicine
hepatitis C viru
Viral
Treatment Failure
Chronic
direct-acting antivirals
resistance test
hepatology
biology
GENOTYPE 1
virus diseases
Middle Aged
Settore MED/07 - Microbiologia e Microbiologia Clinica
Hepatitis C
Italy
Combination
Interferon
Drug Therapy, Combination
Female
030211 gastroenterology & hepatology
Author Keywords:antiviral therapy
RIBAVIRIN
Sequence Analysis
Human
medicine.drug
medicine.medical_specialty
Daclatasvir
Genotype
Hepatitis C virus
Antiviral Agents
LONG-TERM PERSISTENCE
DACLATASVIR
03 medical and health sciences
Drug Therapy
Aged
Drug Resistance, Viral
Hepatitis C, Chronic
Humans
Interferons
Mutation
Ribavirin
Sequence Analysis, DNA
Hepatology
TREATMENT-NAIVE
Internal medicine
Antiviral Agent
resistance-associated substitution
direct-acting antiviral
Hepaciviru
resistance test KeyWords Plus:HEPATITIS-C VIRUS
business.industry
Viral Nonstructural Protein
DNA
biology.organism_classification
Clinical trial
030104 developmental biology
SOFOSBUVIR
chemistry
Sequence Analysi
Immunology
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Liver international, 37 (2017): 514–528. doi:10.1111/liv.13327, info:cnr-pdr/source/autori:Di Maio, Velia C.; Cento, Valeria; Lenci, Ilaria; Aragri, Marianna; Rossi, Piera; Barbaliscia, Silvia; Melis, Michela; Verucchi, Gabriella; Magni, Carlo F.; Teti, Elisabetta; Bertoli, Ada; Antonucci, FrancescoPaolo; Bellocchi, Maria C.; Micheli, Valeria; Masetti, Chiara; Landonio, Simona; Francioso, Simona; Santopaolo, Francesco; Pellicelli, Adriano M.; Calvaruso, Vincenza; Gianserra, Laura; Siciliano, Massimo; Romagnoli, Dante; Cozzolongo, Raffaele; Grieco, Antonio; Vecchiet, Jacopo; Morisco, Filomena; Merli, Manuela; Brancaccio, Giuseppina; Di Biagio, Antonio; Loggi, Elisabetta; Mastroianni, Claudio M.; Palitti, Valeria Pace; Tarquini, Pierluigi; Puoti, Massimo; Taliani, Gloria; Sarmati, Loredana; Picciotto, Antonino; Vullo, Vincenzo; Caporaso, Nicola; Paoloni, Maurizio; Pasquazzi, Caterina; Rizzardini, Giuliano; Parruti, Giustino; Craxi, Antonio; Babudieri, Sergio; Andreoni, Massimo; Angelico, Mario; Perno, Carlo F.; Ceccherini-Silberstein, Francesca; Mariani R, Iapadre N, Grimaldi A, Cozzolongo R, Andreone P, Verucchi G, Menzaghi B, Quirino T, Pisani V, Torti C, Vecchiet J, Bruzzone B, De Maria A, Marenco S, Nicolini LA, Viscoli C, Casinelli K, Delle Monache M, Lichtner M, Aghemo A, Boccaccio V, Bruno S, Cerrone M, Colombo M, D'Arminio Monforte A, Danieli E, Donato F, Gubertini G, Lleo A, Magni CF, Mancon A, Monico S, Niero F, Russo ML, Gnocchi M, Orro A, Milanesi L, Baldelli E, Bertolotti M, Borghi V, Mussini C, Brancaccio G, Gaeta GB, Lembo V, Sangiovanni V, Di Marco V, Mazzola A, Petta S, D'Amico E, Cacciatore P, Consorte A, Pieri A, Polilli E, Sozio F, Antenucci F, Aragri M, Baiocchi L, Barbaliscia S, Biliotti E, Biolato M, Carioti L, Ceccherini-Silberstein F, Cerasari G, Cerva C, Ciotti M, D'Ambrosio C, D'Ettorre G, De Leonardis F, De Sanctis A, Di Maio VC, Di Paolo D, Furlan C, Gallo P, Gasbarrini A, Giannelli V, Grieco S, Lambiase L, Lattanzi B, Lenci I, Lula R, Malagnino V, Manuelli M, Miglioresi L, Milana M, Moretti A, Nosotti L, Palazzo D, Pellicelli A, Romano M, Sarrecchia C, Sforza D, Sorbo MC, Spaziante M, Svicher V, Tisone G, Vespasiani-Gentilucci U, D'Adamo G, Mangia A, Maida I, Mura MS, Falconi L, Di Giammartino D./titolo:Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies/doi:10.1111%2Fliv.13327/rivista:Liver international (Print)/anno:2017/pagina_da:514/pagina_a:528/intervallo_pagine:514–528/volume:37
- Accession number :
- edsair.doi.dedup.....4d63963af4412f1c91789af736ed075a
- Full Text :
- https://doi.org/10.1111/liv.13327