23 results on '"Di Maio, V. C."'
Number of results to display per page
Search Results
2. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels
- Author
-
Di Maio, V. C., Cento, V., Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M. C., Antonucci, F. P., Bertoli, A., Lenci, I., Milana, M., Gianserra, L., Melis, M., Di Biagio, A., Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L. A., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, M., Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C. F., Babudieri, S., Mura, M. S., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, A., Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C. F., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Vecchiet, J., Bruzzone, B., De Maria, A., Di Biagio, A., Marenco, S., Nicolini, L. A., Picciotto, A., Viscoli, C., Casinelli, K., Monache, M. Delle, Lichtner, M., Mastroianni, C., Aghemo, A., Bruno, S., Cerrone, M., Colombo, M., Monforte, A. DʼArminio, Danieli, E., Donato, F., Gubertini, G., Landonio, S., Magni, C. F., Mancon, A., Micheli, V., Monico, S., Niero, F., Puoti, M., Rizzardini, G., Russo, M. L., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Romagnoli, D., Brancaccio, G., Caporaso, N., Gaeta, G. B., Lembo, V., Morisco, F., Calvaruso, V., Craxì, A., Di Marco, V., Mazzola, A., Petta, S., DʼAmico, E., Cacciatore, P., Consorte, A., Palitti, V. Pace, Parruti, G., Pieri, A., Polilli, E., Tontodonati, M., Andreoni, M., Angelico, M., Antenucci, F., Antonucci, F. P., Aragri, M., Armenia, D., Baiocchi, L., Bellocchi, M., Bertoli, A., Biliotti, E., Biolato, M., Carioti, L., Ceccherini-Silberstein, F., Cento, V., Cerasari, G., Cerva, C., Ciotti, M., DʼAmbrosio, C., DʼEttorre, G., De Leonardis, F., De Sanctis, A., Di Maio, V. C., Di Paolo, D., Francioso, S., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Gianserra, L., Grieco, A., Grieco, S., Lambiase, L., Lattanzi, B., Lenci, I., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Milana, M., Nosotti, L., Palazzo, D., Pasquazzi, C., Pellicelli, A., Perno, C. F., Romano, M., Santopaolo, F., Santoro, M. M., Sarmati, L., Sarrecchia, C., Sforza, D., Siciliano, M., Sorbo, M. C., Spaziante, M., Svicher, V., Taliani, G., Teti, E., Tisone, G., Vespasiani-Gentilucci, U., Vullo, V., Mangia, A., Babudieri, S., Maida, I., Melis, M., Mura, M. S., Falconi, L., Di Giammartino, D., and Tarquini, P.
- Published
- 2016
- Full Text
- View/download PDF
3. Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C
- Author
-
Di Maio, V. C., Barbaliscia, S., Teti, E., Fiorentino, G., Milana, M., Paolucci, S., Pollicino, T., Morsica, G., Starace, M., Bruzzone, B., Gennari, W., Micheli, V., Yu La Rosa, K., Foroghi, L., Calvaruso, V., Lenci, I., Polilli, E., Babudieri, S., Aghemo, A., Raimondo, G., Sarmati, L., Coppola, N., Pasquazzi, C., Baldanti, F., Parruti, G., Perno, C. F., Angelico, M., Craxi, A., Andreoni, M., Ceccherini-Silberstein, F., Andreone, P., Aragri, M., Bertoli, A., Boeri, E., Brancaccio, G., Brunetto, M., Callegaro, A. P., Cenderello, G., Cento, V., Ciaccio, A., Ciancio, A., Cuomo, N., De Santis, A., Di Biagio, A., Di Marco, V., Di Perri, G., Di Stefano, M. A., Gaeta, G. B., Ghisetti, V., Gulminetti, R., Lampertico, P., Landonio, S., Lichtner, M., Lleo, A., Maida, I., Marenco, S., Masetti, C., Mastroianni, C., Minichini, C., Milano, E., Monno, L., Novati, S., Pace Palitti, V., Paternoster, C., Pellicelli, A., Pieri, A., Puoti, M., Rizzardini, G., Ruggiero, T., Rossetti, B., Sangiovanni, V., Santantonio, T., Taliani, G., Toniutto, P., Vullo, V., Zazzi, M., Di Maio, V, Barbaliscia, S, Teti, E, Fiorentino, G, Milana, M, Paolucci, S, Pollicino, T, Morsica, G, Starace, M, Bruzzone, B, Gennari, W, Micheli, V, Yu La Rosa, K, Foroghi, L, Calvaruso, V, Lenci, I, Polilli, E, Babudieri, S, Aghemo, A, Raimondo, G, Sarmati, L, Coppola, N, Pasquazzi, C, Baldanti, F, Parruti, G, Perno, C, Angelico, M, Craxi, A, Andreoni, M, Ceccherini-Silberstein, F, Andreone, P, Aragri, M, Bertoli, A, Boeri, E, Brancaccio, G, Brunetto, M, Callegaro, A, Cenderello, G, Cento, V, Ciaccio, A, Ciancio, A, Cuomo, N, De Santis, A, Di Biagio, A, Di Marco, V, Di Perri, G, Di Stefano, M, Gaeta, G, Ghisetti, V, Gulminetti, R, Lampertico, P, Landonio, S, Lichtner, M, Lleo, A, Maida, I, Marenco, S, Masetti, C, Mastroianni, C, Minichini, C, Milano, E, Monno, L, Novati, S, Pace Palitti, V, Paternoster, C, Pellicelli, A, Pieri, A, Puoti, M, Rizzardini, G, Ruggiero, T, Rossetti, B, Sangiovanni, V, Santantonio, T, Taliani, G, Toniutto, P, Vullo, V, Zazzi, M, Di Maio, Vc, Perno, Cf, Craxì, A, Di Maio V.C., Barbaliscia S., Teti E., Fiorentino G., Milana M., Paolucci S., Pollicino T., Morsica G., Starace M., Bruzzone B., Gennari W., Micheli V., Yu La Rosa K., Foroghi L., Calvaruso V., Lenci I., Polilli E., Babudieri S., Aghemo A., Raimondo G., Sarmati L., Coppola N., Pasquazzi C., Baldanti F., Parruti G., Perno C.F., Angelico M., Craxi A., Andreoni M., Ceccherini-Silberstein F., Andreone P., Aragri M., Bertoli A., Boeri E., Brancaccio G., Brunetto M., Callegaro A.P., Cenderello G., Cento V., Ciaccio A., Ciancio A., Cuomo N., De Santis A., Di Biagio A., Di Marco V., Di Perri G., Di Stefano M.A., Gaeta G.B., Ghisetti V., Gulminetti R., Lampertico P., Landonio S., Lichtner M., Lleo A., Maida I., Marenco S., Masetti C., Mastroianni C., Minichini C., Milano E., Monno L., Novati S., Pace Palitti V., Paternoster C., Pellicelli A., Pieri A., Puoti M., Rizzardini G., Ruggiero T., Rossetti B., Sangiovanni V., Santantonio T., Taliani G., Toniutto P., Vullo V., and Zazzi M.
- Subjects
Male ,Sofosbuvir ,Sustained Virologic Response ,Drug Resistance ,Hepacivirus ,Viral Nonstructural Proteins ,Gastroenterology ,Settore MED/06 ,direct-acting antivirals ,failure ,genotype 3 ,HCV ,resistance ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Viral ,Chronic ,Phylogeny ,Dasabuvir ,hcv ,virus diseases ,Hepatitis C ,Pibrentasvir ,Italy ,030220 oncology & carcinogenesis ,Combination ,Drug Therapy, Combination ,030211 gastroenterology & hepatology ,Female ,medicine.drug ,Ledipasvir ,medicine.medical_specialty ,Daclatasvir ,Genotype ,Antiviral Agents ,Drug Resistance, Viral ,Humans ,Hepatitis C, Chronic ,03 medical and health sciences ,Drug Therapy ,Internal medicine ,Antiviral Agent ,direct-acting antiviral ,Hepaciviru ,Hepatology ,business.industry ,Viral Nonstructural Protein ,Glecaprevir ,direct acting antivirals ,Regimen ,chemistry ,Paritaprevir ,business - Abstract
Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N=91/15) and glecaprevir (G)/pibrentasvir (P) (N=9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D±RBV (Paritaprevir/r+Ombitasvir+Dasabuvir, N=15), SOF+Simeprevir (SIM) (N=1) or SOF/Ledipasvir (LDV)±RBV (N=4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P 
- Published
- 2021
4. Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C
- Author
-
Di Maio, V, Barbaliscia, S, Teti, E, Fiorentino, G, Milana, M, Paolucci, S, Pollicino, T, Morsica, G, Starace, M, Bruzzone, B, Gennari, W, Micheli, V, Yu La Rosa, K, Foroghi, L, Calvaruso, V, Lenci, I, Polilli, E, Babudieri, S, Aghemo, A, Raimondo, G, Sarmati, L, Coppola, N, Pasquazzi, C, Baldanti, F, Parruti, G, Perno, C, Angelico, M, Craxi, A, Andreoni, M, Ceccherini-Silberstein, F, Andreone, P, Aragri, M, Bertoli, A, Boeri, E, Brancaccio, G, Brunetto, M, Callegaro, A, Cenderello, G, Cento, V, Ciaccio, A, Ciancio, A, Cuomo, N, De Santis, A, Di Biagio, A, Di Marco, V, Di Perri, G, Di Stefano, M, Gaeta, G, Ghisetti, V, Gulminetti, R, Lampertico, P, Landonio, S, Lichtner, M, Lleo, A, Maida, I, Marenco, S, Masetti, C, Mastroianni, C, Minichini, C, Milano, E, Monno, L, Novati, S, Pace Palitti, V, Paternoster, C, Pellicelli, A, Pieri, A, Puoti, M, Rizzardini, G, Ruggiero, T, Rossetti, B, Sangiovanni, V, Santantonio, T, Taliani, G, Toniutto, P, Vullo, V, Zazzi, M, Di Maio V. C., Barbaliscia S., Teti E., Fiorentino G., Milana M., Paolucci S., Pollicino T., Morsica G., Starace M., Bruzzone B., Gennari W., Micheli V., Yu La Rosa K., Foroghi L., Calvaruso V., Lenci I., Polilli E., Babudieri S., Aghemo A., Raimondo G., Sarmati L., Coppola N., Pasquazzi C., Baldanti F., Parruti G., Perno C. F., Angelico M., Craxi A., Andreoni M., Ceccherini-Silberstein F., Andreone P., Aragri M., Bertoli A., Boeri E., Brancaccio G., Brunetto M., Callegaro A. P., Cenderello G., Cento V., Ciaccio A., Ciancio A., Cuomo N., De Santis A., Di Biagio A., Di Marco V., Di Perri G., Di Stefano M. A., Gaeta G. B., Ghisetti V., Gulminetti R., Lampertico P., Landonio S., Lichtner M., Lleo A., Maida I., Marenco S., Masetti C., Mastroianni C., Minichini C., Milano E., Monno L., Novati S., Pace Palitti V., Paternoster C., Pellicelli A., Pieri A., Puoti M., Rizzardini G., Ruggiero T., Rossetti B., Sangiovanni V., Santantonio T., Taliani G., Toniutto P., Vullo V., Zazzi M., Di Maio, V, Barbaliscia, S, Teti, E, Fiorentino, G, Milana, M, Paolucci, S, Pollicino, T, Morsica, G, Starace, M, Bruzzone, B, Gennari, W, Micheli, V, Yu La Rosa, K, Foroghi, L, Calvaruso, V, Lenci, I, Polilli, E, Babudieri, S, Aghemo, A, Raimondo, G, Sarmati, L, Coppola, N, Pasquazzi, C, Baldanti, F, Parruti, G, Perno, C, Angelico, M, Craxi, A, Andreoni, M, Ceccherini-Silberstein, F, Andreone, P, Aragri, M, Bertoli, A, Boeri, E, Brancaccio, G, Brunetto, M, Callegaro, A, Cenderello, G, Cento, V, Ciaccio, A, Ciancio, A, Cuomo, N, De Santis, A, Di Biagio, A, Di Marco, V, Di Perri, G, Di Stefano, M, Gaeta, G, Ghisetti, V, Gulminetti, R, Lampertico, P, Landonio, S, Lichtner, M, Lleo, A, Maida, I, Marenco, S, Masetti, C, Mastroianni, C, Minichini, C, Milano, E, Monno, L, Novati, S, Pace Palitti, V, Paternoster, C, Pellicelli, A, Pieri, A, Puoti, M, Rizzardini, G, Ruggiero, T, Rossetti, B, Sangiovanni, V, Santantonio, T, Taliani, G, Toniutto, P, Vullo, V, Zazzi, M, Di Maio V. C., Barbaliscia S., Teti E., Fiorentino G., Milana M., Paolucci S., Pollicino T., Morsica G., Starace M., Bruzzone B., Gennari W., Micheli V., Yu La Rosa K., Foroghi L., Calvaruso V., Lenci I., Polilli E., Babudieri S., Aghemo A., Raimondo G., Sarmati L., Coppola N., Pasquazzi C., Baldanti F., Parruti G., Perno C. F., Angelico M., Craxi A., Andreoni M., Ceccherini-Silberstein F., Andreone P., Aragri M., Bertoli A., Boeri E., Brancaccio G., Brunetto M., Callegaro A. P., Cenderello G., Cento V., Ciaccio A., Ciancio A., Cuomo N., De Santis A., Di Biagio A., Di Marco V., Di Perri G., Di Stefano M. A., Gaeta G. B., Ghisetti V., Gulminetti R., Lampertico P., Landonio S., Lichtner M., Lleo A., Maida I., Marenco S., Masetti C., Mastroianni C., Minichini C., Milano E., Monno L., Novati S., Pace Palitti V., Paternoster C., Pellicelli A., Pieri A., Puoti M., Rizzardini G., Ruggiero T., Rossetti B., Sangiovanni V., Santantonio T., Taliani G., Toniutto P., Vullo V., and Zazzi M.
- Abstract
Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P <.001) followed by A30K (12.7% vs 2.8% in DAA-naïve, P <.001). Analysing baseline samples, a higher prevalence of NS5A-RASs was observed before treatment in DAA-failures (5/13, 38.5%) vs DAA-naïves (61/393, 15.5%, P =.04). Regarding 228 DAA-naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A-RASs (P =.002). Conclusions: In this real-life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A-RASs, the most frequent being Y93H. The presence of natu
- Published
- 2021
5. DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018
- Author
-
Redi, D., Rossetti, B., Di Maio, V. C., Aragri, M., Paolucci, S., Masetti, C., Paglicci, L., Bruzzone, B., Minichini, C., FRANCESCA MONTAGNANI, Micheli, V., Landonio, S., Degasperi, E., Giacomo Zanelli, Maserati, R., Maida, I., Callegaro, A. P., Barbaliscia, S., Bertoli, A., Paternoster, C., Marenco, S., Morisco, F., Calvaruso, V., Taliani, G., Puoti, M., Cenderello, G., Santis, A., Lichtner, M., Coppola, N., Gulminetti, R., Cento, V., Rendina, M., Teti, E., Parruti, G., Ruggiero, T., Ghisetti, V., Pasquazzi, C., Nicolini, L. A., Vullo, V., Pellicelli, A., Prestileo, T., Cozzolongo, R., Sangiovanni, V., Biolato, M., Lenci, I., Licata, A., Ciaccio, A., Pace Palitti, V., Giorgini, A., Cariti, G., Ciancio, A., Aghemo, A., Borghi, V., Andreone, P., Brunetto, M., Pollicino, T., Santantonio, T., Cuomo, N., Caudai, C., Babudieri, S., Lampertico, P., Gaeta, G. B., Raimondo, G., Andreoni, M., Rizzardini, G., Angelico, M., Perno, C. F., Craxì, A., Maurizio Zazzi, Ceccherini- Silberstein, F., and on behalf of HCV Virology Italian Resistance Network (Vironet C)
- Published
- 2019
6. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels
- Author
-
Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, Collaborators (129) Mariani R, HCV Italian Resistance Network Study Group., Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio VC, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, Ms, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, HCV Italian Resistance Network Study Group., Collaborators (129) Mariani R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio, Vc, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, M, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V. C, Bellocchi, M. C, Antonucci, F. P, Nicolini, L. A, Magni, C. F, Mura, M. S, Vespasiani Gentilucci, U, Morisco, Filomena, Perno, C. F, Ceccherini Silberstein, F., Caporaso, Nicola, Di Maio, V., Cento, V., Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M., Antonucci, F., Bertoli, A., Lenci, I., Milana, M., Gianserra, L., Melis, M., Di Biagio, A., Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, M., Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C., Babudieri, S., Mura, M., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, A., Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Bruzzone, B., De Maria, A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Mancon, A., Monico, S., Niero, F., Puoti, M., Russo, M., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Caporaso, N., Gaeta, G., Lembo, V., Calvaruso, V., Craxã, A., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pace Palitti, V., Pieri, A., Polilli, E., Antenucci, F., Armenia, D., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Sanctis, A., Furlan, C., Gallo, P., Grieco, A., Grieco, S., Lattanzi, B., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Palazzo, D., Santopaolo, F., Santoro, M., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Teti, E., Mangia, A., Maida, I., Falconi, L., and Di Giammartino, D.
- Subjects
0301 basic medicine ,ns3 ,Genotyping Techniques ,viruses ,Drug Resistance ,Hepacivirus ,Viral Nonstructural Proteins ,medicine.disease_cause ,Gastroenterology ,Telaprevir ,chemistry.chemical_compound ,genotype ,genotyping techniques ,hepacivirus ,hepatitis C ,humans ,RNA viral ,retrospective studies ,sequence analysis ,DNA ,viral nonstructural proteins ,drug resistance, viral ,mutation ,pharmacology ,infectious diseases ,0302 clinical medicine ,Retrospective Studie ,Genotype ,Pharmacology (medical) ,Viral ,Hepatitis C ,Humans ,RNA, Viral ,Retrospective Studies ,Sequence Analysis, DNA ,Drug Resistance, Viral ,Mutation ,Proteolytic enzymes ,virus diseases ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,hcv-rna levels ,Infectious Diseases ,HCV-RNA ,030211 gastroenterology & hepatology ,Sequence Analysis ,medicine.drug ,Human ,Microbiology (medical) ,medicine.medical_specialty ,Hepatitis C virus ,Concordance ,Settore MED/12 - GASTROENTEROLOGIA ,Pharmacology ,Biology ,03 medical and health sciences ,Boceprevir ,Internal medicine ,medicine ,hcv ,Genotyping ,Hepaciviru ,Viral Nonstructural Protein ,Settore MED/09 - MEDICINA INTERNA ,Virology ,digestive system diseases ,030104 developmental biology ,chemistry ,Sequence Analysi ,RNA ,Genotyping Technique - Abstract
OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.
- Published
- 2016
7. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies
- Author
-
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 Maria, Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxì, 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, MARIA CHIARA, Vecchiet, J., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L. A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, Miriam, Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Magni, C. F., Mancon, A., Monico, S., Niero, F., Russo, M. L., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Gaeta, G. B., 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, Elisa, 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, V. C., Di Paolo, D., Furlan, Caterina, 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, Donatella, Pellicelli, A., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M. C., Spaziante, M., Svicher, V., Tisone, G., Vespasiani Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M. S., Falconi, L., Di Giammartino, D., Di Maio, V., Cento, V., Lenci, I., Aragri, M., Rossi, P., Barbaliscia, S., Melis, M., Verucchi, G., Magni, C., Teti, E., Bertoli, A., Antonucci, F., Bellocchi, M., Micheli, V., Masetti, C., Landonio, S., Francioso, S., Santopaolo, F., Pellicelli, A., Calvaruso, V., Gianserra, L., Siciliano, M., Romagnoli, D., Cozzolongo, R., Grieco, A., Vecchiet, J., Morisco, F., Merli, M., Brancaccio, G., Di Biagio, A., Loggi, E., Mastroianni, C., Pace Palitti, V., Tarquini, P., Puoti, M., Taliani, G., Sarmati, L., Picciotto, A., Vullo, V., Caporaso, N., Paoloni, M., Pasquazzi, C., Rizzardini, G., Parruti, G., Craxã¬, A., Babudieri, S., Andreoni, M., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Iapadre, N., Grimaldi, A., Andreone, P., Menzaghi, B., Quirino, T., Pisani, V., Torti, C., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L., 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., Mancon, A., Monico, S., Niero, F., Russo, M., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Gaeta, G., 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., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Paolo, D., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, D., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Tisone, G., Vespasiani-Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M., Falconi, L., Di Giammartino, D., Di Maio, V, Cento, V, Lenci, I, Aragri, M, Rossi, P, Barbaliscia, S, Melis, M, Verucchi, G, Magni, C, Teti, E, Bertoli, A, Antonucci, F, Bellocchi, M, Micheli, V, Masetti, C, Landonio, S, Francioso, S, Santopaolo, F, Pellicelli, A, Calvaruso, V, Gianserra, L, Siciliano, M, Romagnoli, D, Cozzolongo, R, Grieco, A, Morisco, F, Merli, M, Brancaccio, G, Di Biagio, A, Loggi, E, Mastroianni, C, Pace Palitti, V, Tarquini, P, Puoti, M, Taliani, G, Sarmati, L, Picciotto, A, Vullo, V, Caporaso, N, Paoloni, M, Pasquazzi, C, Rizzardini, G, Parruti, G, Craxì, A, Babudieri, S, Andreoni, M, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Velia C. Di Maio, Valeria Cento, Ilaria Lenci, Marianna Aragri, Piera Rossi, Silvia Barbaliscia, Michela Meli, Gabriella Verucchi, Carlo F. Magni, Elisabetta Teti, Ada Bertoli, Francesco Paolo Antonucci, Maria C. Bellocchi, Valeria Micheli, Chiara Masetti, Simona Landonio, Simona Francioso, Francesco Santopaolo, Adriano M. Pellicelli, Vincenza Calvaruso, Laura Gianserra, Massimo Siciliano, Dante Romagnoli, Raffaele Cozzolongo, Antonio Grieco, Jacopo Vecchiet, Filomena Morisco, Manuela Merli, Giuseppina Brancaccio, Antonio Di Biagio, Elisabetta Loggi, Claudio M. Mastroianni, Valeria Pace Palitti, Pierluigi Tarquini, Massimo Puoti, Gloria Taliani, Loredana Sarmati, Antonino Picciotto, Vincenzo Vullo, Nicola Caporaso, Maurizio Paoloni, Caterina Pasquazzi, Giuliano Rizzardini, Giustino Parruti, Antonio Craxì, Sergio Babudieri, Massimo Andreoni, Mario Angelico, Carlo F. Perno, Francesca Ceccherini-Silberstein, for the HCV Italian Resistance Network Study Group: [.., P. Andreone, E. Loggi, G. Verucchi, ], 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., Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxã¬, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini-Silberstein, Francesca, Nicolini, L. A., Magni, C. F., Russo, M. L., Gaeta, G. B., Di Marco, V., Di Maio, V. C., Sorbo, M. C., Mura, M. S., Di Maio, Velia C, Magni, Carlo F, Bellocchi, Maria C, Pellicelli, Adriano M, Mastroianni, Claudio M, Craxì, Antonio, Perno, Carlo F, and Ceccherini Silberstein, Francesca
- 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 - 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.
- Published
- 2017
8. Inferring the migration routes of hepatitis C virus subtype 1a lineages identifies a need for pan-European prevention strategies
- Author
-
Cuypers, L., Vrancken, B., Fabeni, L., Di Maio, V. C., Cento, V., Baele, G., Parczewski, M., Chulanov, V., Gomes, P., Beloukas, A., Geretti, A. M., Dietz, J., Sarrazin, C., Neary, M., Degascun, C., Sierra, S., Kaiser, R., Jimenez, A. B. P., Garcia, F. G., Zazzi, M., Vandamme, A. -M., Silberstein, F. C., Cuypers, L., Vrancken, B., Fabeni, L., Di Maio, V. C., Cento, V., Baele, G., Parczewski, M., Chulanov, V., Gomes, P., Beloukas, A., Geretti, A. M., Dietz, J., Sarrazin, C., Neary, M., Degascun, C., Sierra, S., Kaiser, R., Jimenez, A. B. P., Garcia, F. G., Zazzi, M., Vandamme, A. -M., and Silberstein, F. C.
- Published
- 2018
9. Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy
- Author
-
Bertoli, A, Sorbo, M, Aragri, M, Lenci, I, Teti, E, Polilli, E, Di Maio, V, Gianserra, L, Biliotti, E, Masetti, C, Magni, C, Babudieri, S, Nicolini, L, Milana, M, Cacciatore, P, Sarmati, L, Pellicelli, A, Paolucci, S, Craxi, A, Morisco, F, Palitti, V, Siciliano, M, Coppola, N, Iapadre, N, Puoti, M, Rizzardini, G, Taliani, G, Pasquazzi, C, Andreoni, M, Parruti, G, Angelico, M, Perno, C, Cento, V, Ceccherini-Silberstein, F, Andreone, P, Baldanti, F, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Bruzzone, B, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, D'Ambrosio, C, D'Ettorre, G, De Leonardis, F, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, G, Gasbarrini, A, Ghisetti, V, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Landonio, S, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Melis, M, Menzaghi, B, Meregalli, E, Micheli, V, Niero, F, Paoloni, M, Pieri, A, Rendina, M, Romagnoli, D, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V, Zazzi, M, Bertoli A., Sorbo M. C., Aragri M., Lenci I., Teti E., Polilli E., Di Maio V. C., Gianserra L., Biliotti E., Masetti C., Magni C. F., Babudieri S., Nicolini L. A., Milana M., Cacciatore P., Sarmati L., Pellicelli A., Paolucci S., Craxi A., Morisco F., Palitti V. P., Siciliano M., Coppola N., Iapadre N., Puoti M., Rizzardini G., Taliani G., Pasquazzi C., Andreoni M., Parruti G., Angelico M., Perno C. F., Cento V., Ceccherini-Silberstein F., Andreone P., Baldanti F., Barbarini G., Boccaccio V., Boglione L., Bolis M., Bonora S., Borghi V., Brancaccio G., Bruno S., Bruzzone B., Calvaruso V., Caporaso N., Ciaccio A., Ciancio A., Colombatto P., Cozzolongo R., D'Ambrosio C., D'Ettorre G., De Leonardis F., De Luca A., Di Biagio A., Di Perri G., Francioso S., Gaeta G. B., Gasbarrini A., Ghisetti V., Giorgini A., Grieco A., Gubertini G., Gulminetti R., Lambiase L., Landonio S., Lichtner M., Maida I., Marenco S., Marinaro L., Maserati R., Melis M., Menzaghi B., Meregalli E., Micheli V., Niero F., Paoloni M., Pieri A., Rendina M., Romagnoli D., Rossetti B., Ruggiero T., Sangiovanni V., Starace M., Sticchi L., Tarquini P., Toniutto P., Vullo V., Zazzi M., Bertoli, A, Sorbo, M, Aragri, M, Lenci, I, Teti, E, Polilli, E, Di Maio, V, Gianserra, L, Biliotti, E, Masetti, C, Magni, C, Babudieri, S, Nicolini, L, Milana, M, Cacciatore, P, Sarmati, L, Pellicelli, A, Paolucci, S, Craxi, A, Morisco, F, Palitti, V, Siciliano, M, Coppola, N, Iapadre, N, Puoti, M, Rizzardini, G, Taliani, G, Pasquazzi, C, Andreoni, M, Parruti, G, Angelico, M, Perno, C, Cento, V, Ceccherini-Silberstein, F, Andreone, P, Baldanti, F, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Bruzzone, B, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, D'Ambrosio, C, D'Ettorre, G, De Leonardis, F, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, G, Gasbarrini, A, Ghisetti, V, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Landonio, S, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Melis, M, Menzaghi, B, Meregalli, E, Micheli, V, Niero, F, Paoloni, M, Pieri, A, Rendina, M, Romagnoli, D, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V, Zazzi, M, Bertoli A., Sorbo M. C., Aragri M., Lenci I., Teti E., Polilli E., Di Maio V. C., Gianserra L., Biliotti E., Masetti C., Magni C. F., Babudieri S., Nicolini L. A., Milana M., Cacciatore P., Sarmati L., Pellicelli A., Paolucci S., Craxi A., Morisco F., Palitti V. P., Siciliano M., Coppola N., Iapadre N., Puoti M., Rizzardini G., Taliani G., Pasquazzi C., Andreoni M., Parruti G., Angelico M., Perno C. F., Cento V., Ceccherini-Silberstein F., Andreone P., Baldanti F., Barbarini G., Boccaccio V., Boglione L., Bolis M., Bonora S., Borghi V., Brancaccio G., Bruno S., Bruzzone B., Calvaruso V., Caporaso N., Ciaccio A., Ciancio A., Colombatto P., Cozzolongo R., D'Ambrosio C., D'Ettorre G., De Leonardis F., De Luca A., Di Biagio A., Di Perri G., Francioso S., Gaeta G. B., Gasbarrini A., Ghisetti V., Giorgini A., Grieco A., Gubertini G., Gulminetti R., Lambiase L., Landonio S., Lichtner M., Maida I., Marenco S., Marinaro L., Maserati R., Melis M., Menzaghi B., Meregalli E., Micheli V., Niero F., Paoloni M., Pieri A., Rendina M., Romagnoli D., Rossetti B., Ruggiero T., Sangiovanni V., Starace M., Sticchi L., Tarquini P., Toniutto P., Vullo V., and Zazzi M.
- Abstract
Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2-45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4-19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1-4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.
- Published
- 2018
10. Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?
- Author
-
Di Maio, V, 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, C, Ceccherini-Silberstein, F, 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, Craxi, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, G, 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, L, Palitti, V, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, M, Puoti, M, Rendina, M, Rizzardini, G, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V, Di Maio V. C., 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 C. F., Ceccherini-Silberstein F., 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., Craxi A., D'Ambrosio C., D'Ettorre G., De Luca A., Di Biagio A., Di Perri G., Francioso S., Gaeta G. B., 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 L. A., Palitti V. P., Paoloni M., Parruti G., Pasquazzi C., Pellicelli A., Polilli E., Ponti M. L., Puoti M., Rendina M., Rizzardini G., Rossetti B., Ruggiero T., Sangiovanni V., Starace M., Sticchi L., Tarquini P., Toniutto P., Vullo V., Di Maio, V, 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, C, Ceccherini-Silberstein, F, 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, Craxi, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, G, 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, L, Palitti, V, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, M, Puoti, M, Rendina, M, Rizzardini, G, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V, Di Maio V. C., 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 C. F., Ceccherini-Silberstein F., 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., Craxi A., D'Ambrosio C., D'Ettorre G., De Luca A., Di Biagio A., Di Perri G., Francioso S., Gaeta G. B., 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 L. A., Palitti V. P., Paoloni M., Parruti G., Pasquazzi C., Pellicelli A., Polilli E., Ponti M. L., Puoti M., Rendina M., Rizzardini G., Rossetti B., Ruggiero T., Sangiovanni V., Starace M., Sticchi L., Tarquini P., Toniutto P., and Vullo V.
- Published
- 2018
11. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies
- Author
-
Di Maio, V, Cento, V, Lenci, I, Aragri, M, Rossi, P, Barbaliscia, S, Melis, M, Verucchi, G, Magni, C, Teti, E, Bertoli, A, Antonucci, F, Bellocchi, M, Micheli, V, Masetti, C, Landonio, S, Francioso, S, Santopaolo, F, Pellicelli, A, Calvaruso, V, Gianserra, L, Siciliano, M, Romagnoli, D, Cozzolongo, R, Grieco, A, Morisco, F, Merli, M, Brancaccio, G, Di Biagio, A, Loggi, E, Mastroianni, C, Pace Palitti, V, Tarquini, P, Puoti, M, Taliani, G, Sarmati, L, Picciotto, A, Vullo, V, Caporaso, N, Paoloni, M, Pasquazzi, C, Rizzardini, G, Parruti, G, Craxì, A, Babudieri, S, Andreoni, M, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Di Maio, V. C. a, Cento V. a, Lenci I. b, Aragri, M. a, Rossi P. b, Barbaliscia S. a, Melis M. c, Verucchi G. d, Magni, C. F. e, Teti E. f, Bertoli A, Bellocchi, MC, Pellicelli, AM, Mastroianni, CM, Perno, CF, Di Maio, V, Cento, V, Lenci, I, Aragri, M, Rossi, P, Barbaliscia, S, Melis, M, Verucchi, G, Magni, C, Teti, E, Bertoli, A, Antonucci, F, Bellocchi, M, Micheli, V, Masetti, C, Landonio, S, Francioso, S, Santopaolo, F, Pellicelli, A, Calvaruso, V, Gianserra, L, Siciliano, M, Romagnoli, D, Cozzolongo, R, Grieco, A, Morisco, F, Merli, M, Brancaccio, G, Di Biagio, A, Loggi, E, Mastroianni, C, Pace Palitti, V, Tarquini, P, Puoti, M, Taliani, G, Sarmati, L, Picciotto, A, Vullo, V, Caporaso, N, Paoloni, M, Pasquazzi, C, Rizzardini, G, Parruti, G, Craxì, A, Babudieri, S, Andreoni, M, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Di Maio, V. C. a, Cento V. a, Lenci I. b, Aragri, M. a, Rossi P. b, Barbaliscia S. a, Melis M. c, Verucchi G. d, Magni, C. F. e, Teti E. f, Bertoli A, Bellocchi, MC, Pellicelli, AM, Mastroianni, CM, and Perno, CF
- 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<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥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 HC
- Published
- 2017
12. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels
- Author
-
Di Maio, V, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M, Antonucci, F, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C, Babudieri, S, Mura, M, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Mariani, R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Viscoli, C, Casinelli, K, Delle Monache, M, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, D'Arminio Monforte, A, Danieli, E, Donato, F, Gubertini, G, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, M, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, G, Lembo, V, Calvaruso, V, Craxi, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Pace Palitti, V, Pieri, A, Polilli, E, Antenucci, F, Armenia, D, Baiocchi, L, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Santopaolo, F, Santoro, M, Sforza, D, Sorbo, M, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Falconi, L, Di Giammartino, D, Tarquini, P, Di Maio V. C., Cento V., Di Paolo D., Aragri M., De Leonardis F., Tontodonati M., Micheli V., Bellocchi M. C., Antonucci F. P., Bertoli A., Lenci I., Milana M., Gianserra L., Melis M., Di Biagio A., Sarrecchia C., Sarmati L., Landonio S., Francioso S., Lambiase L., Nicolini L. A., Marenco S., Nosotti L., Giannelli V., Siciliano M., Romagnoli D., Pellicelli A., Vecchiet J., Magni C. F., Babudieri S., Mura M. S., Taliani G., Mastroianni C., Vespasiani-Gentilucci U., Romano M., Morisco F., Gasbarrini A., Vullo V., Bruno S., Baiguera C., Pasquazzi C., Tisone G., Picciotto A., Andreoni M., Parruti G., Rizzardini G., Angelico M., Perno C. F., Ceccherini-Silberstein F., Mariani R., Paoloni M., Iapadre N., Grimaldi A., Menzaghi B., Quirino T., Bruzzone B., De Maria A., Viscoli C., Casinelli K., Delle Monache M., Lichtner M., Aghemo A., Cerrone M., Colombo M., D'Arminio Monforte A., Danieli E., Donato F., Gubertini G., Mancon A., Monico S., Niero F., Puoti M., Russo M. L., Alfieri R., Gnocchi M., Orro A., Milanesi L., Baldelli E., Bertolotti M., Borghi V., Mussini C., Brancaccio G., Caporaso N., Gaeta G. B., Lembo V., Calvaruso V., Craxi A., Di Marco V., Mazzola A., Petta S., D'Amico E., Cacciatore P., Consorte A., Pace Palitti V., Pieri A., Polilli E., Antenucci F., Armenia D., Baiocchi L., Biliotti E., Biolato M., Carioti L., Cerasari G., Cerva C., Ciotti M., D'Ambrosio C., D'Ettorre G., De Sanctis A., Furlan C., Gallo P., Grieco A., Grieco S., Lattanzi B., Malagnino V., Manuelli M., Merli M., Miglioresi L., Palazzo D., Santopaolo F., Santoro M. M., Sforza D., Sorbo M. C., Spaziante M., Svicher V., Teti E., Mangia A., Maida I., Falconi L., Di Giammartino D., Tarquini P., Di Maio, V, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M, Antonucci, F, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C, Babudieri, S, Mura, M, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Mariani, R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Viscoli, C, Casinelli, K, Delle Monache, M, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, D'Arminio Monforte, A, Danieli, E, Donato, F, Gubertini, G, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, M, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, G, Lembo, V, Calvaruso, V, Craxi, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Pace Palitti, V, Pieri, A, Polilli, E, Antenucci, F, Armenia, D, Baiocchi, L, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Santopaolo, F, Santoro, M, Sforza, D, Sorbo, M, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Falconi, L, Di Giammartino, D, Tarquini, P, Di Maio V. C., Cento V., Di Paolo D., Aragri M., De Leonardis F., Tontodonati M., Micheli V., Bellocchi M. C., Antonucci F. P., Bertoli A., Lenci I., Milana M., Gianserra L., Melis M., Di Biagio A., Sarrecchia C., Sarmati L., Landonio S., Francioso S., Lambiase L., Nicolini L. A., Marenco S., Nosotti L., Giannelli V., Siciliano M., Romagnoli D., Pellicelli A., Vecchiet J., Magni C. F., Babudieri S., Mura M. S., Taliani G., Mastroianni C., Vespasiani-Gentilucci U., Romano M., Morisco F., Gasbarrini A., Vullo V., Bruno S., Baiguera C., Pasquazzi C., Tisone G., Picciotto A., Andreoni M., Parruti G., Rizzardini G., Angelico M., Perno C. F., Ceccherini-Silberstein F., Mariani R., Paoloni M., Iapadre N., Grimaldi A., Menzaghi B., Quirino T., Bruzzone B., De Maria A., Viscoli C., Casinelli K., Delle Monache M., Lichtner M., Aghemo A., Cerrone M., Colombo M., D'Arminio Monforte A., Danieli E., Donato F., Gubertini G., Mancon A., Monico S., Niero F., Puoti M., Russo M. L., Alfieri R., Gnocchi M., Orro A., Milanesi L., Baldelli E., Bertolotti M., Borghi V., Mussini C., Brancaccio G., Caporaso N., Gaeta G. B., Lembo V., Calvaruso V., Craxi A., Di Marco V., Mazzola A., Petta S., D'Amico E., Cacciatore P., Consorte A., Pace Palitti V., Pieri A., Polilli E., Antenucci F., Armenia D., Baiocchi L., Biliotti E., Biolato M., Carioti L., Cerasari G., Cerva C., Ciotti M., D'Ambrosio C., D'Ettorre G., De Sanctis A., Furlan C., Gallo P., Grieco A., Grieco S., Lattanzi B., Malagnino V., Manuelli M., Merli M., Miglioresi L., Palazzo D., Santopaolo F., Santoro M. M., Sforza D., Sorbo M. C., Spaziante M., Svicher V., Teti E., Mangia A., Maida I., Falconi L., Di Giammartino D., and Tarquini P.
- Abstract
Objectives: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. Methods: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. Results: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA > 3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤ 3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). Conclusions: HCV-NS3 sequencing provides reliable
- Published
- 2016
13. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels
- Author
-
Di Maio, V. C., primary, Cento, V., additional, Di Paolo, D., additional, Aragri, M., additional, De Leonardis, F., additional, Tontodonati, M., additional, Micheli, V., additional, Bellocchi, M. C., additional, Antonucci, F. P., additional, Bertoli, A., additional, Lenci, I., additional, Milana, M., additional, Gianserra, L., additional, Melis, M., additional, Di Biagio, A., additional, Sarrecchia, C., additional, Sarmati, L., additional, Landonio, S., additional, Francioso, S., additional, Lambiase, L., additional, Nicolini, L. A., additional, Marenco, S., additional, Nosotti, L., additional, Giannelli, V., additional, Siciliano, M., additional, Romagnoli, D., additional, Pellicelli, A., additional, Vecchiet, J., additional, Magni, C. F., additional, Babudieri, S., additional, Mura, M. S., additional, Taliani, G., additional, Mastroianni, C., additional, Vespasiani-Gentilucci, U., additional, Romano, M., additional, Morisco, F., additional, Gasbarrini, A., additional, Vullo, V., additional, Bruno, S., additional, Baiguera, C., additional, Pasquazzi, C., additional, Tisone, G., additional, Picciotto, A., additional, Andreoni, M., additional, Parruti, G., additional, Rizzardini, G., additional, Angelico, M., additional, Perno, C. F., additional, and Ceccherini-Silberstein, F., additional
- Published
- 2015
- Full Text
- View/download PDF
14. Key genetic signatures in the whole pre-S1/Pre-S2/s gene correlate eith HBV-induced carcinogenesis by affecting HBsAG secretion and release
- Author
-
Andreoni, M., Sarrecchia, C., Cento, V., Bertoli, A., Angelico, M., Vecchiet, J., Mari, T., Iapadre, N., Salpini, R., Verheyen, Jens, Aragri, M., Alteri, C., Pasquazzi, C., Svicher, V., Gori, C., Gubertini, G., Fleury, H., Perno, C.-F., Neumann-Fraune, M., Barlattani, A., Trimoulet, P., Di Maio, V.-C., Mirabelli, C., Ceccherini-Silberstein, F., and Micheli, V.
- Subjects
Medizin - Published
- 2013
15. KEY GENETIC MARKERS IN THE FULL-LENGTH HBSAG GENE CORRELATE WITH HBV-DRIVEN CARCINOGENESIS BY AFFECTING HBSAG SECRETION AND RELEASE
- Author
-
Svicher, V., Neumann-Fraunea, M., Mirabelli, C., Salpini, R., Cento, V., Di Maio, V. C., Pollicita, M., Bertoli, A., Alteri, C., Aragri, M., Gori, C., Santoro, M. M., Salso, A., Rizzardini, G., Gubertini, G., Micheli, V., Niero, F., Magni, C., Trimoulet, P., Fleury, H., Vecchiet, J., Iapadre, N., Barlattani, A., Mario, T., Pasquazzi, C., Missale, G., Sarrecchia, C., Ceccherini-Silberstein, F., Andreoni, M., Angelico, M., Verhejen, J., Perno, C. F., Svicher, V., Neumann-Fraunea, M., Mirabelli, C., Salpini, R., Cento, V., Di Maio, V. C., Pollicita, M., Bertoli, A., Alteri, C., Aragri, M., Gori, C., Santoro, M. M., Salso, A., Rizzardini, G., Gubertini, G., Micheli, V., Niero, F., Magni, C., Trimoulet, P., Fleury, H., Vecchiet, J., Iapadre, N., Barlattani, A., Mario, T., Pasquazzi, C., Missale, G., Sarrecchia, C., Ceccherini-Silberstein, F., Andreoni, M., Angelico, M., Verhejen, J., and Perno, C. F.
- Published
- 2014
16. Hepatitis C Virus Genetic Variability and the Presence of NS5B Resistance-Associated Mutations as Natural Polymorphisms in Selected Genotypes Could Affect the Response to NS5B Inhibitors
- Author
-
Di Maio, V. C., primary, Cento, V., additional, Mirabelli, C., additional, Artese, A., additional, Costa, G., additional, Alcaro, S., additional, Perno, C. F., additional, and Ceccherini-Silberstein, F., additional
- Published
- 2014
- Full Text
- View/download PDF
17. 430 KEY GENETIC SIGNATURES IN THE WHOLE pre-S1/Pre-S2/S GENE CORRELATE WITH HBV-INDUCED CARCINOGENESIS BY AFFECTING HBsAg SECRETION AND RELEASE
- Author
-
Svicher, V., primary, Neumann-Fraune, M., additional, Mirabelli, C., additional, Salpini, R., additional, Cento, V., additional, Di Maio, V.-C., additional, Bertoli, A., additional, Alteri, C., additional, Aragri, M., additional, Gori, C., additional, Micheli, V., additional, Gubertini, G., additional, Trimoulet, P., additional, Fleury, H., additional, Vecchiet, J., additional, Iapadre, N., additional, Barlattani, A., additional, Mari, T., additional, Pasquazzi, C., additional, Sarrecchia, C., additional, Ceccherini-Silberstein, F., additional, Andreoni, M., additional, Angelico, M., additional, Verheyen, J., additional, and Perno, C.-F., additional
- Published
- 2013
- Full Text
- View/download PDF
18. May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics
- Author
-
Tontodonati, M., Valeria Cento, Polilli, E., Colabattista, C., Cascella, R., Sciotti, M. P., Di Giammartino, D., Trave, F., Di Maio, V. C., Monarca, R., Di Candilo, F., Prinapori, R., Rastrelli, E., Vecchiet, J., Ceccherini-Silberstein, F., Manzoli, L., Giardina, E., Perno, C. F., and Parruti, G.
- Subjects
Adult ,Male ,RVR ,Genotype ,Early viral kinetics ,Hepacivirus ,Antiviral Agents ,Polymorphism, Single Nucleotide ,Cohort Studies ,Young Adult ,Ribavirin ,Humans ,EVR ,HCV dual therapy ,HCV therapy optimization ,Interleukins ,Interferon-alpha ,Middle Aged ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Hepatitis C ,Kinetics ,Treatment Outcome ,Italy ,Drug Therapy, Combination ,Female ,Interferons - Abstract
When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 482 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.
19. Clinical usefulness of HCV sequencing on clinical samples with different HCV-RNA levels
- Author
-
Ceccherini-Silberstein, F., Di Maio, V. C., Cento, V., Di Paolo, D., Aragri, M., Leonardis, F., Tontodonati, M., Valeria Micheli, Antonucci, F. P., Campoli, R., Mancon, A., Bertoli, A., Lenci, I., Cucchiarelli, S., Manunta, A., Di Biagio, A., Sarrecchia, C., Nicolini, L. A., Marenco, S., Ciotti, M., Nosotti, L., Gianelli, V., Merli, M., Siciliano, M., Landonio, S., Maria, A., Pellicelli, A., Vecchiet, J., Magni, C., Babudieri, S., Mura, M. S., Taliani, G., Lichtner, M., Maida, I., Vespasiani, U., Romano, M., Morisco, F., Gasbarrini, A., Mastroianni, C., Puoti, M., Mangia, A., Bruno, S., Tisone, G., Caporaso, N., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., and Perno, C. F.
20. KEY PATTERNS OF HBX AND PRE-S1/S2 MUTATIONS ARE INVOLVED IN MECHANISMS UNDERLYING HBV-INDUCED HEPATOCELLULAR CARCINOMA IN VIVO
- Author
-
Svicher, V., Mirabelli, C., Valeria Cento, Salpini, R., Di Maio, V. C., Bertoli, A., Alteri, C., Pollicita, M., Gori, C., Micheli, V., Salso, A., Gubertini, G., Trimoulet, P., Fleury, H., Vecchiet, J., Iapadre, N., Barlattani, A., Mari, T., Pasquazzi, C., Sarrechia, C., Ceccherini-Silberstein, F., Andreoni, M., Angelico, M., and Perno, C. F.
- Subjects
Settore MED/07 - Microbiologia e Microbiologia Clinica
21. Declino delle Sostituzioni associate a resistenza (RAS) ad inibitori di NS3 ed NS5A al fallimento con DAA nel virus dell’epatite C in Italia negli anni 2015-2018
- Author
-
Paglicci, L., Redi, D., Rossetti, B., Di Maio, V. C., Aragri, M., Paolucci, S., Masetti, C., Bruzzone, B., Minichini, C., FRANCESCA MONTAGNANI, Micheli, V., Landonio, S., Degasperi, E., Giacomo Zanelli, Maserati, R., Maida, I., Callegaro, A. P., Barbaliscia, S., Bertoli, A., Paternoster, C., Marenco, S., Morisco, F., Calvaruso, V., Taliani, G., Puoti, M., Cenderello, G., Santis, A., Lichtner, M., Coppola, N., Gulminetti, R., Cento, V., Rendina, M., Teti, E., Parruti, G., Ruggiero, T., Ghisetti, V., Pasquazzi, C., Nicolini, L. A., Vullo, V., Pellicelli, A., Prestileo, T., Cozzolongo, R., Sangiovanni, V., Biolato, M., Lenci, I., Licata, A., Ciaccio, A., Pace Palitti, V., Giorgini, A., Cariti, G., Ciancio, A., Aghemo, A., Borghi, V., Andreone, P., Brunetto, M., Pollicino, T., Santantonio, T., Cuomo, N., Caudai, C., Babudieri, S., Lampertico, P., Gaeta, G. B., Raimondo, G., Andreoni, M., Rizzardini, G., Angelico, M., Perno, C. F., Craxì, A., Maurizio Zazzi, and Ceccherini-Silberstein, F.
22. NOVEL REVERSE TRANSCRIPTASE MUTATIONS SPECIFICALLY ASSOCIATED WITH SELECTED ANTI-HBV TREATMENT CAN INDUCE ALTERATIONS AND STOP-CODONS IN HBV S ANTIGEN
- Author
-
Valeria Cento, Hemert, F., Di Maio, V. C., Salpini, R., Mirabelli, C., Bertoli, A., Gori, C., Micheli, V., Gubertini, G., Longo, R., Romano, S., Visca, M., Sanctis, G. M., Marino, N., Mazzotta, F., Cappiello, G., Sarrecchia, C., Ceccherini-Silberstein, F., Andreoni, M., Angelico, M., Perno, C. F., and Svicher, V.
- Subjects
Settore MED/07 - Microbiologia e Microbiologia Clinica
23. Successful ongoing retreatment with glecaprevir/pibrentasvir + sofosbuvir + ribavirin in a patient with HCV genotype 3 who failed glecaprevir/pibrentasvir with both NS3 and NS5A resistance.
- Author
-
Aragri M, Milana M, Di Maio VC, Lenci I, Carioti L, Perno CF, Svicher V, Angelico M, and Ceccherini-Silberstein F
- Subjects
- Drug Therapy, Combination, Genotype, Hepacivirus drug effects, Hepatitis C diagnosis, Hepatitis C virology, Humans, Leucine therapeutic use, Male, Middle Aged, Proline therapeutic use, Pyrrolidines, Treatment Outcome, Aminoisobutyric Acids therapeutic use, Antiviral Agents therapeutic use, Benzimidazoles therapeutic use, Cyclopropanes therapeutic use, Hepacivirus genetics, Hepatitis C drug therapy, Lactams, Macrocyclic therapeutic use, Leucine analogs & derivatives, Proline analogs & derivatives, Quinoxalines therapeutic use, Sofosbuvir therapeutic use, Sulfonamides therapeutic use
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.