220 results on '"Gulminetti, R."'
Search Results
102. Durability of Dolutegravir-Based Regimens: A 5-Year Prospective Observational Study
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Lucia, Taramasso, Andrea, De Vito, Elena Delfina, Ricci, Giancarlo, Orofino, Nicola, Squillace, Barbara, Menzaghi, Chiara, Molteni, Roberto, Gulminetti, Giuseppe Vittorio, De Socio, Giovanni Francesco, Pellicanò, Eleonora, Sarchi, Benedetto Maurizio, Celesia, Leonardo, Calza, Stefano, Rusconi, Laura, Valsecchi, Canio Vito, Martinelli, Antonio, Cascio, Paolo, Maggi, Francesca, Vichi, Goffredo, Angioni, Giuliana, Guadagnino, Giovanni, Cenderello, Chiara, Dentone, Alessandra, Bandera, Katia, Falasca, Paolo, Bonfanti, Antonio, Di Biagio, Giordano, Madeddu, M, Guastavigna, Taramasso, L., De Vito, A., Ricci, E. D., Orofino, G., Squillace, N., Menzaghi, B., Molteni, C., Gulminetti, R., De Socio, G. V., Pellicano, G. F., Sarchi, E., Celesia, B. M., Calza, L., Rusconi, S., Valsecchi, L., Martinelli, C. V., Cascio, A., Maggi, P., Vichi, F., Angioni, G., Guadagnino, G., Cenderello, G., Dentone, C., Bandera, A., Falasca, K., Bonfanti, P., Di Biagio, A., Madeddu, G., Taramasso L, De Vito A, Ricci ED, Orofino G, Squillace N, Menzaghi B, Molteni C, Gulminetti R, De Socio GV, Pellicanò GF, Sarchi E, Celesia BM, Calza L, Rusconi S, Valsecchi L, Martinelli CV, Cascio A, Maggi P, Vichi F, Angioni G, Guadagnino G, Cenderello G, Dentone C, Bandera A, Falasca K, Bonfanti P, Di Biagio A, Madeddu G, Taramasso L., De Vito A., Ricci E.D., Orofino G., Squillace N., Menzaghi B., Molteni C., Gulminetti R., De Socio G.V., Pellicano G.F., Sarchi E., Celesia B.M., Calza L., Rusconi S., Valsecchi L., Martinelli C.V., Cascio A., Maggi P., Vichi F., Angioni G., Guadagnino G., Cenderello G., Dentone C., Bandera A., Falasca K., Bonfanti P., Di Biagio A., Madeddu G., Taramasso, L, De Vito, A, Ricci, E, Orofino, G, Squillace, N, Menzaghi, B, Molteni, C, Gulminetti, R, De Socio, G, Pellicanò, G, Sarchi, E, Celesia, B, Calza, L, Rusconi, S, Valsecchi, L, Martinelli, C, Cascio, A, Maggi, P, Vichi, F, Angioni, G, Guadagnino, G, Cenderello, G, Dentone, C, Bandera, A, Falasca, K, Bonfanti, P, Di Biagio, A, and Madeddu, G
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adverse events ,dolutegravir ,durability ,HIV ,safety ,toxicity ,virolgical failure ,Cohort Studies ,Female ,Heterocyclic Compounds, 3-Ring ,Humans ,Middle Aged ,Oxazines ,Piperazines ,Prospective Studies ,Pyridones ,Anti-HIV Agents ,HIV Infections ,Pediatrics ,medicine.medical_specialty ,Settore MED/17 - Malattie Infettive ,Oxazine ,Human immunodeficiency virus (HIV) ,adverse event ,Pyridone ,medicine.disease_cause ,3-Ring ,chemistry.chemical_compound ,Heterocyclic Compounds ,Antiretroviral treatment ,Medicine ,Adverse effect ,Piperazine ,business.industry ,Public Health, Environmental and Occupational Health ,Anti-HIV Agent ,Discontinuation ,Prospective Studie ,Infectious Diseases ,chemistry ,Dolutegravir ,Observational study ,Cohort Studie ,business ,Human - Abstract
This study evaluates the frequency and causes of dolutegravir (DTG) discontinuation along 5 years of follow-up, in both antiretroviral treatment (ART)-naive and experienced people living with HIV (PLWH). This is a prospective multi-center cohort study enrolling PLWH on DTG from July 2014 until November 2020. DTG-durability was investigated using the Kaplan-Meier survival curve. The Cox proportional-hazards model was used for estimating the hazard ratio (HR) of DTG discontinuation for any cause, and for adverse events (AEs). Nine hundred sixty-three PLWH were included, 25.3% were women and 28.0% were ART-naive. Discontinuations for any causes were 10.1 [95% confidence interval (95% CI) 8.9-11.5] per 100 person-years, similar in most regimens, with the apparent exception of tenofovir alafenamide/emtricitabine+DTG (p
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- 2021
103. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort
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Maria Giovanna Quaranta, Luigina Ferrigno, Xhimi Tata, Franca D'Angelo, Marco Massari, Carmine Coppola, Elisa Biliotti, Alessia Giorgini, Diletta Laccabue, Alessia Ciancio, Pier Luigi Blanc, Marzia Margotti, Donatella Ieluzzi, Maurizia Rossana Brunetto, Francesco Barbaro, Francesco Paolo Russo, Ilaria Beretta, Giulia Morsica, Gabriella Verucchi, Annalisa Saracino, Massimo Galli, Loeta A. Kondili, Cesare Mazzaro, Manuela Bertola, Ornella Schioppa, Antonio Benedetti, Laura Schiadà, Monica Cucco, Andrea Giacometti, Laura Brescini, Sefora Castelletti, Alessandro Fiorentini, Gioacchino Angarano, Michele Milella, Alfredo Di Leo, Maria Rendina, Fulvio Salvatore D'abramo, Chiara Lillo, Andrea Iannone, Mariano Piazzolla, Lorenzo Badia, Fabio Piscaglia, Francesca Benevento, Ilaria Serio, Francesco Castelli, Serena Zaltron, Angiola Spinetti, Silvia Odolini, Raffaele Bruno, Mario Mondelli, Luchino Chessa, Martina Loi, Carlo Torti, Chiara Costa, Maria Mazzitelli, Vincenzo Pisani, Vincenzo Scaglione, Enrico Maria Trecarichi, Anna Linda Zignego, Monica Monti, Francesco Madia, Letizia Attala, Piera Pierotti, Elena Salomoni, Elisa Mariabelli, Teresa Antonia Santantonio, Serena Rita Bruno, Ester Marina Cela, Matteo Bassetti, Giovanni Mazzarello, Anna Ida Alessandrini, Antonio Di Biagio, Laura Ambra Nicolini, Giovanni Raimondo, Roberto Filomia, Alessio Aghemo, Rossella Meli, Adriano Lazzarin, Stefania Salpietro, Anna Ludovica Fracanzani, Erika Fatta, Rosa Lombardi, Pietro Lampertico, Marta Borghi, Roberta D'ambrosio, Elisabetta Degasperi, Massimo Puoti, Chiara Baiguera, Federico D'amico, Maria Vinci, Maria Grazia Rumi, Massimo Zuin, Paola Zermiani, Pietro Andreone, Paolo Caraceni, Valeria Guarneri, Erica Villa, Veronica Bernabucci, Laura Bristot, Maria Luisa Paradiso, Guglielmo Migliorino, Alessandra Gambaro, Giuseppe Lapadula, Anna Spolti, Alessandro Soria, Pietro Invernizzi, Antonio Ciaccio, Martina LucÀ, Federica Malinverno, Laura Ratti, Daniela Caterina Amoruso, Federica Pisano, Ferdinando Scarano, Laura Staiano, Filomena Morisco, Valentina Cossiga, Ivan Gentile, Antonio Riccardo Buonomo, Maria Foggia, Emanuela Zappulo, Alessandro Federico, Marcello Dallio, Nicola Coppola, Caterina Sagnelli, Salvatore Martini, Caterina Monari, Gerardo Nardone, Costantino Sgamato, Liliana Chemello, Luisa Cavalletto, Daniela Sterrantino, Alberto Zanetto, Paola Zanaga, Giuseppina Brancaccio, Antonio Craxì, Salvatore Petta, Vincenza Calvaruso, Luciano Crapanzano, Salvatore Madonia, Marco Cannizzaro, Erica Maria Bruno, Anna Licata, Simona Amodeo, Adele Rosaria Capitano, Carlo Ferrari, Elisa Negri, Alessandra Orlandini, Marco Pesci, Roberto Gulminetti, Layla Pagnucco, Giustino Parruti, Paola Di Stefano, Barbara Coco, Romina Corsini, Elisa Garlassi, Massimo Andreoni, Elisabetta Teti, Carlotta Cerva, Lorenzo Baiocchi, Giuseppe Grassi, Antonio Gasbarrini, Maurizio Pompili, Martina De Siena, Gloria Taliani, Martina Spaziante, Marcello Persico, Mario Masarone, Andrea Aglitti, Gemma Calvanese, Marco Anselmo, Pasqualina De Leo, Monica Marturano, Giorgio Maria Saracco, Quaranta M.G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P.L., Margotti M., Ieluzzi D., Brunetto M.R., Barbaro F., Russo F.P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L.A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A.D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E.M., Zignego A.L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T.A., Bruno S.R., Cela E.M., Bassetti M., Mazzarello G., Alessandrini A.I., Biagio A.D., Nicolini L.A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A.L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M.G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M.L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D.C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A.R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E.M., Licata A., Amodeo S., Capitano A.R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P.D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M.D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P.D., Marturano M., Saracco G.M., Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta, M. G., Ferrigno, L., Tata, X., D'Angelo, F., Massari, M., Coppola, C., Biliotti, E., Giorgini, A., Laccabue, D., Ciancio, A., Blanc, P. L., Margotti, M., Ieluzzi, D., Brunetto, M. R., Barbaro, F., Russo, F. P., Beretta, I., Morsica, G., Verucchi, G., Saracino, A., Galli, M., Kondili, L. A., Mazzaro, C., Bertola, M., Benedetti, A., Schiada, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Fiorentini, A., Angarano, G., Milella, M., Leo, A. D., Rendina, M., Salvatore D'ABRAMO, F., Lillo, C., Iannone, A., Piazzolla, M., Badia, L., Piscaglia, F., Benevento, F., Serio, I., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Bruno, R., Mondelli, M., Chessa, L., Loi, M., Torti, C., Costa, C., Mazzitelli, M., Pisani, V., Scaglione, V., Trecarichi, E. M., Zignego, A. L., Monti, M., Madia, F., Attala, L., Pierotti, P., Salomoni, E., Mariabelli, E., Santantonio, T. A., Bruno, S. R., Cela, E. M., Bassetti, M., Mazzarello, G., Alessandrini, A. I., Biagio, A. D., Nicolini, L. A., Raimondo, G., Filomia, R., Aghemo, A., Meli, R., Lazzarin, A., Salpietro, S., Fracanzani, A. L., Fatta, E., Lombardi, R., Lampertico, P., Borghi, M., D'Ambrosio, R., Degasperi, E., Puoti, M., Baiguera, C., D'Amico, F., Vinci, M., Rumi, M. G., Zuin, M., Zermiani, P., Andreone, P., Caraceni, P., Guarneri, V., Villa, E., Bernabucci, V., Bristot, L., Paradiso, M. L., Migliorino, G., Gambaro, A., Lapadula, G., Spolti, A., Soria, A., Invernizzi, P., Ciaccio, A., Luca, M., Malinverno, F., Ratti, L., Amoruso, D. C., Pisano, F., Scarano, F., Staiano, L., Morisco, F., Cossiga, V., Gentile, I., Buonomo, A. R., Foggia, M., Zappulo, E., Federico, A., Dallio, M., Coppola, N., Sagnelli, C., Martini, S., Monari, C., Nardone, G., Sgamato, C., Chemello, L., Cavalletto, L., Sterrantino, D., Zanetto, A., Zanaga, P., Brancaccio, G., Craxi, A., Petta, S., Calvaruso, V., Crapanzano, L., Madonia, S., Cannizzaro, M., Bruno, E. M., Licata, A., Amodeo, S., Capitano, A. R., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Gulminetti, R., Pagnucco, L., Parruti, G., Stefano, P. D., Coco, B., Corsini, R., Garlassi, E., Andreoni, M., Teti, E., Cerva, C., Baiocchi, L., Grassi, G., Gasbarrini, A., Pompili, M., Siena, M. D., Taliani, G., Spaziante, M., Persico, M., Masarone, M., Aglitti, A., Calvanese, G., Anselmo, M., Leo, P. D., Marturano, M., and Saracco, G. M.
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Male ,HCV genotypes ,Ethnic group ,Linked-to-care patient ,Comorbidity ,Hepacivirus ,Logistic regression ,medicine.disease_cause ,Comorbidities ,Direct acting antivirals ,HCV Cohort ,Linked-to-care patients ,Aged ,Antiviral Agents ,Coinfection ,Female ,Hepatitis C, Chronic ,Humans ,Italy ,Middle Aged ,Transients and Migrants ,0302 clinical medicine ,Medicine ,Chronic ,Gastroenterology ,virus diseases ,Hepatitis C ,Life evaluation ,030220 oncology & carcinogenesis ,Cohort ,030211 gastroenterology & hepatology ,Comorbiditie ,Human ,Hepatitis C virus ,Settore MED/12 - GASTROENTEROLOGIA ,03 medical and health sciences ,Disease severity ,Antiviral Agent ,Hepaciviru ,Hepatology ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,medicine.disease ,digestive system diseases ,Direct acting antiviral ,business ,Demography - Abstract
Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.
- Published
- 2021
104. Discontinuation of treatment and adverse events in an Italian cohort of patients on dolutegravir
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Paolo Bonfanti, Stefano Rusconi, Paola Vitiello, Nicola Squillace, Roberto Gulminetti, Benedetto Maurizio Celesia, Giancarlo Orofino, Elena Ricci, Paolo Maggi, Giordano Madeddu, Bonfanti, P, Madeddu, G, Gulminetti, R, Squillace, N, Orofino, G, Vitiello, P, Rusconi, S, Celesia, B, Maggi, P, Ricci, E, Bonfanti, P., Madeddu, G., Gulminetti, R., Squillace, N., Orofino, G., Vitiello, P., Rusconi, S., Celesia, B. M., Maggi, P., and Ricci, E.
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0301 basic medicine ,medicine.medical_specialty ,030106 microbiology ,Immunology ,Human immunodeficiency virus (HIV) ,MEDLINE ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Immunology and Allergy ,HIV Infection ,030212 general & internal medicine ,Adverse effect ,business.industry ,HIV ,Discontinuation ,HIV Integrase Inhibitor ,Infectious Diseases ,chemistry ,Dolutegravir ,Cohort ,HIV Integrase Inhibitors ,Cohort Studie ,business ,Heterocyclic Compounds, 3-Ring ,Human ,Cohort study - Published
- 2017
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105. Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?
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Velia Chiara Di Maio, Valeria Cento, Marianna Aragri, Stefania Paolucci, Teresa Pollicino, Nicola Coppola, Bianca Bruzzone, Valeria Ghisetti, Maurizio Zazzi, Maurizia Brunetto, Ada Bertoli, Silvia Barbaliscia, Silvia Galli, William Gennari, Fausto Baldanti, Giovanni Raimondo, Carlo Federico Perno, Francesca Ceccherini-Silberstein, Pietro Andreone, Massimo Andreoni, Mario Angelico, Sergio Babudieri, Giorgio Barbarini, Vincenzo Boccaccio, Lucio Boglione, Matteo Bolis, Stefano Bonora, Vanni Borghi, Giuseppina Brancaccio, Savino Bruno, Pierluigi Cacciatore, Vincenza Calvaruso, Nicola Caporaso, Antonio Ciaccio, Alessia Ciancio, Piero Colombatto, Raffaele Cozzolongo, Antonio Craxì, Cecilia D'Ambrosio, Gabriella D'Ettorre, Andrea De Luca, Antonio Di Biagio, Giovanni Di Perri, Simona Francioso, Giovanni Battista Gaeta, Alessia Giorgini, Antonio Grieco, Guido Gubertini, Roberto Gulminetti, Lara Lambiase, Ilaria Lenci, Miriam Lichtner, Ivana Maida, Simona Marenco, Letizia Marinaro, Renato Maserati, Chiara Masetti, Michela Melis, Elisa Meregalli, Valeria Micheli, Filomena Morisco, Fosca Niero, Laura Ambra Nicolini, Valeria Pace Palitti, Maurizio Paoloni, Giustino Parruti, Caterina Pasquazzi, Adriano Pellicelli, Ennio Polilli, Maria Laura Ponti, Massimo Puoti, Maria Rendina, Giuliano Rizzardini, Barbara Rossetti, Tina Ruggiero, Vincenzo Sangiovanni, Mario Starace, Laura Sticchi, Pierluigi Tarquini, Pierluigi Toniutto, Vincenzo Vullo, Di Maio VC, Cento V, Aragri M, Paolucci S, Pollicino T3, Coppola N4, Bruzzone B5, Ghisetti V6, Zazzi M7, Brunetto M8, Bertoli A1, Barbaliscia S1, Galli S9, Gennari W10, Baldanti F2, Raimondo G3, Perno CF1, Ceccherini-Silberstein F11, 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 Vincenza, Caporaso N, Ciaccio A, Ciancio A, Colombatto P, Cozzolongo R, Craxì Antonio, D'Ambrosio C, D'Ettorre G, De Luca A, Di Biagio A, Di Perri G, Francioso S, Gaeta GB, 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 LA, Palitti VP, Paoloni M, Parruti G, Pasquazzi C, Pellicelli A, Polilli E, Ponti ML, Puoti M, Rendina M, Rizzardini G, Rossetti B, Ruggiero T, Sangiovanni V, Starace M, Sticchi L, Tarquini P, Toniutto P, Vullo V., Di Maio, Vc, 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, Cf, 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, Craxì, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, Gb, 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, La, Palitti, Vp, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, Ml, 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, Perno, C, Ceccherini-Silberstein, F, Andreone, P, Craxi, A, Gaeta, G, Nicolini, L, Palitti, V, Ponti, M, and Vullo, V
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0301 basic medicine ,medicine.medical_specialty ,hepacivirus ,HCV RAS ,Treatment outcome ,Drug Resistance ,HCV genotypes ,Drug resistance ,Biology ,NS5A ,03 medical and health sciences ,0302 clinical medicine ,Second line ,drug resistance viral ,humans ,retreatment ,treatment outcome ,antiviral agents ,hepatitis c chronic ,Internal medicine ,Drug Resistance, Viral ,Humans ,Retreatment ,Treatment Outcome ,Antiviral Agents ,Hepacivirus ,Hepatitis C, Chronic ,medicine ,Viral ,Chronic ,Hepatology ,Hepatitis C ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,medicine.disease ,Virology ,Hepatology, HCV, NS5A ,030104 developmental biology ,HCV ,030211 gastroenterology & hepatology - Published
- 2018
106. Incident diabetes in course of antiretroviral therapy
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Taramasso, Lucia, Squillace, Nicola, Ricci, Elena, Menzaghi, Barbara, Orofino, Giancarlo, Socio, Giuseppe Vittorio De, Molteni, Chiara, Martinelli, Canio Vito, Madeddu, Giordano, Vichi, Francesca, Valsecchi, Laura, Celesia, Benedetto Maurizio, Maggi, Paolo, Rusconi, Stefano, Pellicanò, Giovanni Francesco, Cascio, Antonio, Sarchi, Eleonora, Gulminetti, Roberto, Falasca, Katia, Di Biagio, Antonio, Bonfanti, Paolo, Taramasso, L, Squillace, N, Ricci, E, Menzaghi, B, Orofino, G, Socio, G, Molteni, C, Martinelli, C, Madeddu, G, Vichi, F, Valsecchi, L, Celesia, B, Maggi, P, Rusconi, S, Pellicanò, G, Cascio, A, Sarchi, E, Gulminetti, R, Falasca, K, Di Biagio, A, Bonfanti, P, Taramasso, Lucia, Squillace, Nicola, Ricci, Elena, Menzaghi, Barbara, Orofino, Giancarlo, Socio, Giuseppe Vittorio De, Molteni, Chiara, Martinelli, Canio Vito, Madeddu, Giordano, Vichi, Francesca, Valsecchi, Laura, Celesia, Benedetto Maurizio, Maggi, Paolo, Rusconi, Stefano, Pellicanò, Giovanni Francesco, Cascio, Antonio, Sarchi, Eleonora, Gulminetti, Roberto, Falasca, Katia, Di Biagio, Antonio, and Bonfanti, Paolo
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protease inhibitor ,metabolic health ,obesity ,Infectious Diseases ,diabete ,insulin resistance ,Immunology ,Immunology and Allergy ,integrase inhibitor ,weight gain - Abstract
Objective:Recent reports of excessive weight gain in people with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitors (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset.Design:Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort.Methods:All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM.Results:4366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4+ 460 [interquartile range (IQR) 256-710] cells/mm3cells/mm3. During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05-1.50).Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 kg 1.03; 95% CI 1.01-1.04), as well as older age (aHR 1.03 by 1 year; 95% CI 1.01-1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95% CI 1.48-3.49), having untreated high blood pressure (aHR 2.90; 95% CI 1.30-6.45) and baseline blood glucose >100 mg/dl (aHR 5.47; 95% CI 3.82-7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM.Conclusions:Baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort.
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- 2023
107. Trajectories of CD4+/CD8+ T-Cells Ratio 96 Weeks after Switching to Dolutegravir-Based Two-Drug Regimens: Results from a Multicenter Prospective Cohort Study
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Lucia Taramasso, Antonio Falletta, Elena Ricci, Giancarlo Orofino, Nicola Squillace, Barbara Menzaghi, Giuseppe Vittorio De Socio, Chiara Molteni, Giovanni Francesco Pellicanò, Roberto Gulminetti, Giordano Madeddu, Eleonora Sarchi, Francesca Vichi, Benedetto Maurizio Celesia, Paolo Bonfanti, Antonio Di Biagio, Taramasso, L, Falletta, A, Ricci, E, Orofino, G, Squillace, N, Menzaghi, B, De Socio, G, Molteni, C, Pellicanò, G, Gulminetti, R, Madeddu, G, Sarchi, E, Vichi, F, Celesia, B, Bonfanti, P, and Di Biagio, A
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dolutegravir ,two-drug regimen ,three-drug regimen ,ART ,immune recovery ,CD4/CD8 ratio ,Infectious Diseases ,Virology - Abstract
The aim of the present study was to evaluate CD4/CD8 dynamics in patients on dolutegravir (DTG)-based two-drug regimens (2DRs) and compare them with DTG-containing triple-drug regimens (3DRs). A prospective observational study was performed in the context of the SCOLTA cohort. Experienced PWH with HIV-RNA < 50 copies/mL were included if they were on the DTG-2DR, the DTG + tenofovir/emtricitabine (TDF/FTC) regimen, the DTG + tenofovir alafenamide (TAF)/FTC regimen, or the DTG + abacavir/lamivudine (ABC/3TC) regimen; they were followed-up for at least one year. A total of 533 PWH were enrolled, 120 in the DTG + 3TC group, 38 in the DTG + protease inhibitors (PI) group, 67 in the DTG + rilpivirine (RPV) group, 49 in the DTG + TDF/FTC group, 27 in the DTG + TAF/FTC group, and 232 in the DTG + ABC/3TC group. After one year, the CD4/CD8 ratio significantly increased in the PWH treated with DTG + 3TC (+0.08 ± 0.26), DTG + TDF/FTC (+0.1 ± 0.19), and DTG + ABC/3TC (+0.08 ± 0.25). At two years, the CD4/CD8 increase was confirmed for PWH on DTG + TDF/FTC (+0.16 ± 0.28) and DTG + ABC/3TC (+0.1 ± 0.3). In the SCOLTA cohort, PWH on 2DRs experienced a CD4/CD8 increase only in the DTG + 3TC group. Controlled studies with longer follow-up will clarify the long-term immunological and clinical impacts of DTG-2DR.
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- 2022
108. Invecchiare con la terapia antiretrovirale o essere anziani in terapia antiretrovirale: due profili di comorbidità differenti?
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Verdiana Zollo, Barbara Menzaghi, Chiara Molteni, Nicola Squillace, Lucia Taramasso, Ilaria De Luca, Giulia Gamboni, Debora Altobelli, Marta Guastavigna, Giordano Madeddu, Francesca Vichi9 Antonio Cascio, Eleonora Sarchi, Giovanni Pellicanò, Canio Martinelli, Benedetto Maurizio Celesia, Laura Valsecchi, Roberto Gulminetti, Giovanni Cenderello, Andrea Parisini, Leonardo Calza, Katia Falasca, Antonio Di Biagio, Paolo Bonfanti, Giancarlo Orofino, Paolo Maggi., Zollo, V, Menzaghi, B, Molteni, C, Squillace, N, Taramasso, L, De Luca, I, Gamboni, G, Altobelli, D, Guastavigna, M, Madeddu, G, Vichi9 Antonio Cascio, F, Sarchi, E, Pellicanò, G, Martinelli, C, Maurizio Celesia, B, Valsecchi, L, Gulminetti, R, Cenderello, G, Parisini, A, Calza, L, Falasca, K, Di Biagio, A, Bonfanti, P, Orofino, G, and Maggi., P
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ART duration ,multimorbidity ,age ,HIV - Abstract
Nelle persone che vivono con HIV (PLWH), il peso delle patologie corniche non trasmissibili è aumentato nel tempo, a causa dell’invecchiamento legato a una maggiore sopravvivenza, all’infiammazione cronica, all’attivazione del sistema immunitario, e all’esposizione a lungo termine alla terapia antiretrovirale (ART). L’età anagrafica, quella alla diagnosi di infezione da HIV, e l’esposizione alla ART sono fattori che possono esercitare un effetto sulle differenze sia qualitative che quantitative tra le comorbidità.Per esplorare questa ipotesi, abbiamo valutato la prevalenza di alcune patologie selezionate nei pazienti arruolati nel progetto SCOLTA, per gruppi di età (50-59 e ≥60 anni) e durata della ART. In 1336 soggetti (23.9% donne), la durata della ART era simile tra gruppi di età, sia considerata in continuo (p=0.85) che in categorie (p=0.88). Come atteso, le comorbidità e la multimorbidità erano meno frequenti nel gruppo 50-59 che in quello ≥60 anni. Gli odds ratios (ORs) aggiustati per sesso ed età hanno mostrato che, nella categoria 50-59, si rilevava un aumento di rischio significativo e coerente in categorie di durata della ART, per le malattie cardiovascolari (CVD) (ORs da 1.68 a 2.18), dislipidemia (ORs da 3.61 a 9.08) e osteopenia/osteoporosi (ORs da 3.74 a 6.23). Di conseguenza, anche il rischio di multimorbidità aumentava attraverso le classi di durata della ART (ORs da 2.04 a 4.40). Nel gruppo ≥60 anni, il rischio CVD era significativamente più elevato solo nei pazienti con durata della ART ≥20 anni (OR 2.61, 95% intervallo di confidenza al 95% 1.22-5.58, categoria di riferimento ≤6 mesi). L’aumento di dislipidemia e multimorbidità era coerentemente associato con una maggiore durata della ART.In conclusione, l’età anagrafica, quella alla diagnosi di infezione da HIV, e l’esposizione alla ART sono associate alla multi-morbidità nelle PLWH.
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- 2022
109. Plasma Levels of Bacterial DNA in HIV Infection: The Limits of Quantitative Polymerase Chain Reaction
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Claudio Bandi, Stefano Novati, Emanuele Ferri, Maurizio Casiraghi, F. Genco, Roberto Gulminetti, Vittorio Sambri, Ferri E., Novati S., Casiraghi M., Sambri V., Genco F., Gulminetti R., Bandi C., Ferri, E, Novati, S, Casiraghi, M, Sambri, V, Genco, F, Gulminetti, R, and Bandi, C
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BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Human immunodeficiency virus (HIV) ,HIV ,QtPCR ,Plasma levels ,technique ,Biology ,medicine.disease_cause ,Virology ,Molecular biology ,BROAD RANGE PCR ,BACTERIAL DNA ,Infectious Diseases ,Real-time polymerase chain reaction ,HIV INFECTION ,medicine ,Immunology and Allergy ,viral infection ,BACTERIEMIA ,Bacterial dna - Published
- 2010
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110. Fattori associati con il ricovero ospedaliero per COVID-19 in 80 pazienti HIV-positivi italiani. Factors associated with hospital admission for COVID-19 in 80 Italian HIV patients
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Lucia Taramasso, Leonardo Calza, Nicola Squillace, Barbara Menzaghi, Stefano Rusconi, 5 Andrea Parisini, Giancarlo Orofino, Olivia Bargiacchi, Roberto Gulminetti, Molteni Chiara, Laura Valsecchi, Giovanni Cenderello, Sergio Ferrara, Paolo Maggi, Annalisa Saracino, Katia Falasca, Antonio Di Biagio, Paolo Bonfanti, Taramasso, L, Calza, L, Squillace, N, Menzaghi, B, Rusconi, S, Andrea Parisini, 5, Orofino, G, Bargiacchi, O, Gulminetti, R, Chiara, M, Valsecchi, L, Cenderello, G, Ferrara, S, Maggi, P, Saracino, A, Falasca, K, Di Biagio, A, and Bonfanti, P
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hospital admission ,SARS-CoV-2 ,COVID-19 ,HIV - Abstract
Questo studio analizza i ricoveri ospedalieri e l’outcome di 80 pazienti HIV-positivi, con diagnosi di infezione da SARS-CoV-2 effettuata tra febbraio e settembre 2020, in una rete di centri di Malattie Infettive italiani. Sesso, etnia e durata dell’infezione da HIV e dei trattamenti antiretrovirali (ART) erano simili nei soggetti ricoverati e non, mentre i 45 pazienti ricoverati erano più vecchi, avevano valori più bassi sia per quanto riguarda il nadir dei CD4 che la conta dei linfociti al momento della diagnosi. Questi due valori erano anche correlati ad un esito peggiore della COVID-19. Durante il periodo di osservazione, 10 (12.3%) pazienti sono morti. La terapia ART non sembrava associata con la severità della malattia da SARS-CoV-2. This study reports on hospital admission and outcomes of 80 HIV-infected subjects who were diagnosed with SARSCoV-2 infection between February and September 2020, in a network of Italian centers. Sex, ethnicity and duration of HIV infection and antiretroviral therapy (ART) were similar in admitted and non-admitted subjects, whereas 45 admitted patients were older, had lower nadir CD4 cells and current lymphocytes count. These values were also correlated to worse COVID-19 outcome. Ten (12.3%) patients died over the observation period. ART drugs did not seem associated with disease severity.
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- 2021
111. Lipid profile improvement in virologically suppressed HIV-1-infected patients switched to dolutegravir/abacavir/lamivudine: data from the SCOLTA project
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Nicola Squillace, Lucia Taramasso, Benedetto Maurizio Celesia, Elena Ricci, Giancarlo Orofino, Giuseppe Vittorio De Socio, Paolo Bonfanti, Giordano Madeddu, Roberto Gulminetti, Giovanni Francesco Pellicanò, Barbara Menzaghi, Chiara Dentone, Paola Bagella, Bagella, P, Squillace, N, Ricci, E, Gulminetti, R, De Socio, G, Taramasso, L, Pellicanò, G, Menzaghi, B, Celesia, B, Dentone, C, Orofino, G, Bonfanti, P, and Madeddu, G
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0301 basic medicine ,medicine.medical_specialty ,030106 microbiology ,Human immunodeficiency virus (HIV) ,HIV-1 infection ,HIV-1 infection, dolutegravir/abacavir/lamivudine, lipid profile ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,medicine ,Pharmacology (medical) ,In patient ,030212 general & internal medicine ,Original Research ,Pharmacology ,Reverse-transcriptase inhibitor ,medicine.diagnostic_test ,business.industry ,Abacavir/Lamivudine ,medicine.disease ,lipid profile ,Regimen ,Dolutegravir/abacavir/lamivudine ,Lipid profile ,Infectious Diseases ,chemistry ,Infection and Drug Resistance ,Dolutegravir ,dolutegravir/abacavir/lamivudine ,lipids (amino acids, peptides, and proteins) ,business ,medicine.drug - Abstract
Paola Bagella,1 Nicola Squillace,2 Elena Ricci,3 Roberto Gulminetti,4 Giuseppe Vittorio De Socio,5 Lucia Taramasso,6 Giovanni Pellicanò,7 Barbara Menzaghi,8 Benedetto Maurizio Celesia,9 Chiara Dentone,10 Giancarlo Orofino,11 Paolo Bonfanti,12 Giordano Madeddu13On behalf of the C.I.S.A.I. Study Group, Italy1Unit of Post-acute Long Term Care, ATS Sardegna, Sassari, Italy; 2Infectious Diseases Unit, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy; 3Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy; 4Unit of Infectious Diseases, IRCCS San Matteo Hospital, Pavia, Italy; 5Infectious Diseases Unit Department of Medicine, Azienda Ospedaliero-Universitaria di Perugia, Santa Maria Hospital, Perugia, Italy; 6Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca‘ Granda Ospedale Maggiore Policlinico, Milan, Italy; 7Department of Human Pathology of the Adult and the Developmental Age ‘G. Barresi‘, Unit of Infectious Diseases, University of Messina, Messina, Italy; 8Unit of Infectious Diseases, ASST della Valle Olona, Busto Arsizio, Italy; 9Unit of Infectious Diseases, Garibaldi Hospital, Catania, Italy; 10Unit of Infectious Diseases, Sanremo Hospital, Sanremo, Italy; 11Unit of Infectious Diseases, Amedeo di Savoia Hospital, Turin, Italy; 12Unit of Infectious Diseases, A. Manzoni Hospital, Lecco, Italy; 13Unit of Infectious Diseases, Department of Clinical, Surgical and Experimental Medicine, University of Sassari, Sassari, ItalyIntroduction: Metabolic disorders are common amongst HIV-infected patients. Data from real-life setting on the impact of DTG/ABC/3TC in virologically suppressed HIV-infected patients are scarce.Methods: We investigated the modification of metabolic profile including fasting glucose, lipid profile and markers of insulin resistance (IR) in experienced patients switching from a boosted protease inhibitors (bPI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to DTG/ABC/3TC in a prospective, observational, multicenter study.Results: We enrolled 131 HIV-infected patients, of whom 91 (69.5%) males, mean age was 50.5±10.6 years. CDC stage was A in 66 (50.4%) patients, of whom 91 (69.5%) had acquired HIV through sexual contacts. The previous regimen was bPI-based in 79 patients (60.3%) and NNRTI-based in 52 (39.7%). Patients switching from NNRTI showed a significant reduction at week 24 in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL). Triglycerides/high-density lipoprotein cholesterol (TG/HDL) ratio, HDL, median TG and TG/HDL ratio did not show significant modification during follow-up times. Among patients switching from a bPI, we observed a significant reduction in TC and LDL at both follow-up times and a slight increase in HDL. Triglycerides/HDL ratio, median TG and TG/HDL ratio showed a decrease over time that became significant at weeks 24 and 48. Blood glucose levels did not significantly vary during the observation period in patients switching from both bPI and NNRTI-based regimens.Conclusion: Our data suggest an improvement in lipid profile and TG/HDL ratio in pretreated HIV-1-infected patients who switched to DTG/ABC/3TC over 48 weeks, especially in those previously receiving a bPI-based regimen.Keywords: HIV-1 infection, dolutegravir/abacavir/lamivudine, lipid profile
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- 2019
112. Switch to dolutegravir and unboosted atazanavir in HIV-1 infected patients with undetectable viral load and long exposure to antiretroviral therapy
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Andrea Poli, Agostino Riva, Simona Di Giambenedetto, Roberto Gulminetti, Antonella Castagna, Sinibaldo Carosella, Giovanni Mazzola, Stefano Bonora, Anna Maria Cattelan, Stefano Rusconi, Laura Galli, Maria Eugenia Quiros-Roldan, Giuseppe Vittorio De Socio, Maurizio Mena, Nicoletta Ladisa, Castagna, A., Rusconi, S., Gulminetti, R., Bonora, S., Mazzola, G., Quiros-Roldan, M. E., De Socio, G. V., Ladisa, N., Carosella, S., Cattelan, A., Di Giambenedetto, S., Mena, M., Poli, A., Galli, L., and Riva, A.
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0301 basic medicine ,Male ,HIV Infections ,Kaplan-Meier Estimate ,Piperazines ,chemistry.chemical_compound ,0302 clinical medicine ,Antiretroviral Therapy, Highly Active ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Drug Substitution ,Health Policy ,virus diseases ,Middle Aged ,Viral Load ,dolutegravir ,Treatment Outcome ,Infectious Diseases ,Dolutegravir ,RNA, Viral ,Drug Therapy, Combination ,Female ,Viral load ,Heterocyclic Compounds, 3-Ring ,medicine.drug ,medicine.medical_specialty ,Pyridones ,Immunology ,Atazanavir Sulfate ,antiretroviral therapy ,switch strategy ,Settore MED/17 - MALATTIE INFETTIVE ,03 medical and health sciences ,Pharmacotherapy ,Internal medicine ,Oxazines ,Humans ,HIV Integrase Inhibitors ,dual therapy ,business.industry ,Antiretroviral therapy ,Discontinuation ,Atazanavir ,CD4 Lymphocyte Count ,Regimen ,030104 developmental biology ,chemistry ,HIV-1 ,business - Abstract
We evaluated the efficacy and safety of a two-drug regimen including dolutegravir (DTG) and unboosted atazanavir (uATV) in 151 HIV-1 infected patients with HIV-RNA of more than 50 copies/ml. During a median follow-up of 62 (42-97) weeks, two virological failures (1%) and 13 treatment discontinuations (9%) occurred; the 48-week probability of virological failure was 0.8% (95% confidence interval 0.2-5.6%). Switch to DTG + uATV may represent a boosting and transcriptase reverse inhibitors sparing otion in individuals with long exposure to antiretroviral therapy and risk of cardiovascular disease.
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- 2019
113. Dolutegravir safety in a real-life setting: results Title from the SCOLTA cohort
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G. Madeddu, M. S. Mameli, N. Squillace, B. Menzaghi, R. Gulminetti, G. V. De Socio, A. Di Biagio, G. C. Orofino, G. Pellicanò, B. M. Celesia, L. Calza, C. Martinelli, S. Rusconi, A. Cascio, F. Vichi, G. Cenderello, L. Valsecchi, P. Maggi, G. Angioni, C. Dentone, K. Falasca, E. Ricci, P. Bonfanti, Castagna A, D'Arminio A, Puoti M, Rizzardini G., Madeddu, G., Mameli, M. S., Squillace, N., Menzaghi, B., Gulminetti, R., De Socio, G. V., Di Biagio, A., Orofino, G. C., Pellicanò, G., Celesia, B. M., Calza, L., Martinelli, C., Rusconi, S., Cascio, A., Vichi, F., Cenderello, G., Valsecchi, L., Maggi, P., Angioni, G., Dentone, C., Falasca, K., Ricci, E., and Bonfanti, P.
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- 2019
114. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials
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Pedro Cahn, Juan Sierra Madero, José Ramón Arribas, Andrea Antinori, Roberto Ortiz, Amanda E Clarke, Chien-Ching Hung, Jürgen K Rockstroh, Pierre-Marie Girard, Jörg Sievers, Choy Man, Alexander Currie, Mark Underwood, Allan R Tenorio, Keith Pappa, Brian Wynne, Anna Fettiplace, Martin Gartland, Michael Aboud, Kimberly Smith, Lidia Cassetti, Daniel David, Laura Figueras, Marcelo Losso, Gustavo Lopardo, Sergio Lupo, Norma Porteiro, Marisa Sánchez, Mark Bloch, David Cooper, Robert Finlayson, Anthony Kelleher, Kenneth Koh, David Lewis, James McMahon, Richard Moore, Norman Roth, Matthew Shields, Stephane De Wit, Eric Florence, Jean-Christophe Goffard, Remy Demeester, Patrick Lacor, Bernard Vandercam, Linos Vandekerckhove, Jonathan Angel, Jean-Guy Baril, Brian Conway, Alexandra De Pokomandy, Jason Szabo, Sharon Walmsley, Olivier Bouchaud, Christian Chidiac, Pierre Delobel, Cecile Goujard, Christine Katlama, Jean-Michel Molina, Gilles Pialoux, Patrick Philibert, Johannes Bogner, Stefan Esser, Ivanka Krznaric, Clara Lehmann, Christoph Spinner, Hans-Jurgen Stellbrink, Christoph Stephan, Albrecht Stoehr, Enrico Barchi, Pietro Caramello, Francesco Castelli, Anna Maria Cattelan, Antonella D'Arminio Monforte, Antonio Di Biagio, Giovanni Di Perri, Andrea Gori, Franco Maggiolo, Barbara Menzaghi, Guglielmo Migliorino, Cristina Mussini, Giovanni Penco, Massimo Puoti, Giuliano Rizzardini, Roberto Gulminetti, Adriano Lazzarin, Tiziano Quirino, Laura Sighinolfi, Pierluigi Viale, Gerardo Amaya Tapia, Jaime Andrade Villanueva, Enrique R Granados Reyes, Alma Perez Rios, Mario Santoscoy Gomez, Jan Den Hollander, Bart Rijnders, José A Hidalgo, Luis Hercilla Vasquez, Luis Illescas, Anita Olczak, Kamal Mansinho, Patricia Paula Correia Pacheco, Eugénio Teófilo, Jose Saraiva da Cunha, Rui Sarmento e Castro, Rosário Serrão, Manuela Arbune, Cristian Jianu, Anca Oprea, Liliana Preotescu, Liviu-Jany Prisacariu, Elena Belonosova, Olga Borodkina, Oxana Chernova, Natalia Gankina, Svetlana Kizhlo, Valeriy Kulagin, Nadezhda Kurina, Firaya Nagimova, Vadim Pokrovsky, Elena Ryamova, Evgeny Voronin, Alexey Yakovlev, Richard Kaplan, Sun Hee Lee, Shin-Woo Kim, Sang-Il Kim, Woo Joo Kim, Antonio Antela Lopez, Jose L Casado Osorio, Manuel A Castaño Carracedo, Ignacio De Los Santos Gil, Vicente Estrada Perez, Vicenç Falco Ferrer, Luis Force, Maria Jose Galinda Puerto, Miguel Garcia Deltoro, Josep M Gatell, Miguel A Goenaga Sanchez, Ana González Cordón, Hernando Knobel, Juan Carlos Lopez Bernaldo de Quiros, Juan E Losa Garcia, Mar Masia, Marta Montero-Alsonso, Antonio Ocampo Hermida, Juan Pasquau Liaño, Joaquin Portilla Sogorb, Federico Pulido Ortega, Antonio Rivera Roman, Jose Ramon Santos Fernandez, Rafael Torres Perea, Jesus Troya Garcia, Pompeyo Viciana Fernandez, Alexandra Calmy, Christoph Hauser, Jan Fehr, Shu-Hsing Cheng, Wen-Chien Ko, Hsi-Hsun Lin, Po-Liang Lu, Yu-Ting Tseng, Ning-Chi Wang, Wing-Wai Wong, Chia-Jui Yang, Roberto Arduino, Paul Benson, Mezgebe Berhe, Fritz Bredeek, Cynthia Brinson, Thomas Campbell, Gordon Crofoot, Douglas Cunningham, Edwin DeJesus, Robin Dretler, Joseph Eron, Kenneth Fife, Carl Fichtenbaum, Jason Flamm, Deborah Goldstein, Samir Gupta, Debbie Hagins, Margaret Hoffman-Terry, Dushyantha Jayaweera, Clifford Kinder, Daniel Klein, Cheryl McDonald, Anthony Mills, Ronald Nahass, Olayemi Osiyemi, Edgar Overton, David Parks, David Prelutsky, Moti Ramgopal, Shannon Schrader, Beverly Sha, Gary Simon, James Sims, Daniel Skiest, Jihad Slim, Karen Tashima, Blair Thedinger, Brian Gazzard, Julie Fox, Margaret Johnson, Stephen Kegg, Saye Khoo, Charles Mazhude, Chloe Orkin, Gabriel Schembri, Andrew Ustianowski, Clinical sciences, Microbiology and Infection Control, Internal Medicine, Cahn, P, Madero, J, Arribas, J, Antinori, A, Ortiz, R, Clarke, A, Hung, C, Rockstroh, J, Girard, P, Sievers, J, Man, C, Currie, A, Underwood, M, Tenorio, A, Pappa, K, Wynne, B, Fettiplace, A, Gartland, M, Aboud, M, Smith, K, Cassetti, L, David, D, Figueras, L, Losso, M, Lopardo, G, Lupo, S, Porteiro, N, Sanchez, M, Bloch, M, Cooper, D, Finlayson, R, Kelleher, A, Koh, K, Lewis, D, Mcmahon, J, Moore, R, Roth, N, Shields, M, De Wit, S, Florence, E, Goffard, J, Demeester, R, Lacor, P, Vandercam, B, Vandekerckhove, L, Angel, J, Baril, J, Conway, B, De Pokomandy, A, Szabo, J, Walmsley, S, Bouchaud, O, Chidiac, C, Delobel, P, Goujard, C, Katlama, C, Molina, J, Pialoux, G, Philibert, P, Bogner, J, Esser, S, Krznaric, I, Lehmann, C, Spinner, C, Stellbrink, H, Stephan, C, Stoehr, A, Barchi, E, Caramello, P, Castelli, F, Cattelan, A, D'Arminio Monforte, A, Di Biagio, A, Di Perri, G, Gori, A, Maggiolo, F, Menzaghi, B, Migliorino, G, Mussini, C, Penco, G, Puoti, M, Rizzardini, G, Gulminetti, R, Lazzarin, A, Quirino, T, Sighinolfi, L, Viale, P, Amaya Tapia, G, Andrade Villanueva, J, Granados Reyes, E, Perez Rios, A, Santoscoy Gomez, M, Den Hollander, J, Rijnders, B, Hidalgo, J, Hercilla Vasquez, L, Illescas, L, Olczak, A, Mansinho, K, Correia Pacheco, P, Teofilo, E, Saraiva da Cunha, J, Sarmento e Castro, R, Serrao, R, Arbune, M, Jianu, C, Oprea, A, Preotescu, L, Prisacariu, L, Belonosova, E, Borodkina, O, Chernova, O, Gankina, N, Kizhlo, S, Kulagin, V, Kurina, N, Nagimova, F, Pokrovsky, V, Ryamova, E, Voronin, E, Yakovlev, A, Kaplan, R, Lee, S, Kim, S, Kim, W, Antela Lopez, A, Casado Osorio, J, Castano Carracedo, M, De Los Santos Gil, I, Estrada Perez, V, Falco Ferrer, V, Force, L, Galinda Puerto, M, Garcia Deltoro, M, Gatell, J, Goenaga Sanchez, M, Gonzalez Cordon, A, Knobel, H, Lopez Bernaldo de Quiros, J, Losa Garcia, J, Masia, M, Montero-Alsonso, M, Ocampo Hermida, A, Pasquau Liano, J, Portilla Sogorb, J, Pulido Ortega, F, Rivera Roman, A, Santos Fernandez, J, Torres Perea, R, Troya Garcia, J, Viciana Fernandez, P, Calmy, A, Hauser, C, Fehr, J, Cheng, S, Ko, W, Lin, H, Lu, P, Tseng, Y, Wang, N, Wong, W, Yang, C, Arduino, R, Benson, P, Berhe, M, Bredeek, F, Brinson, C, Campbell, T, Crofoot, G, Cunningham, D, Dejesus, E, Dretler, R, Eron, J, Fife, K, Fichtenbaum, C, Flamm, J, Goldstein, D, Gupta, S, Hagins, D, Hoffman-Terry, M, Jayaweera, D, Kinder, C, Klein, D, Mcdonald, C, Mills, A, Nahass, R, Osiyemi, O, Overton, E, Parks, D, Prelutsky, D, Ramgopal, M, Schrader, S, Sha, B, Simon, G, Sims, J, Skiest, D, Slim, J, Tashima, K, Thedinger, B, Gazzard, B, Fox, J, Johnson, M, Kegg, S, Khoo, S, Mazhude, C, Orkin, C, Schembri, G, and Ustianowski, A
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Male ,HIV Dolutegravir ,HIV Infections ,030204 cardiovascular system & hematology ,Piperazines ,chemistry.chemical_compound ,0302 clinical medicine ,Abacavir ,Heterocyclic Compounds ,Emtricitabine ,030212 general & internal medicine ,Viral ,Tenofovir/adverse effects ,Lamivudine/adverse effects ,Medicine(all) ,education.field_of_study ,Adult ,Anti-HIV Agents ,Anti-Retroviral Agents ,Double-Blind Method ,Drug Therapy, Combination ,Female ,HIV-1 ,Heterocyclic Compounds, 3-Ring ,Humans ,Lamivudine ,Middle Aged ,RNA, Viral ,Tenofovir ,Viral Load ,Heterocyclic Compounds, 3-Ring/adverse effects ,General Medicine ,Emtricitabine/adverse effects ,Tolerability ,Dolutegravir ,Combination ,medicine.drug ,medicine.medical_specialty ,Pyridones ,Population ,HIV Infections/drug therapy ,Anti-Retroviral Agents/adverse effects ,3-Ring ,03 medical and health sciences ,Drug Therapy ,SDG 3 - Good Health and Well-being ,Internal medicine ,Oxazines ,medicine ,HIV-1/isolation & purification ,RNA, Viral/blood ,education ,business.industry ,Viral Load/drug effects ,Regimen ,chemistry ,RNA ,Anti-HIV Agents/adverse effects ,Ritonavir ,business - Abstract
Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.
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- 2019
115. Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA)
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Taramasso, L., Tatarelli, Paola, Ricci, Elena, Madeddu, G., Menzaghi, B., Squillace, Nicola, De Socio, G. V., Martinelli, C., Gulminetti, Roberto, Maggi, P., Orofino, G., Vichi, F., Di Biagio, A., Bonfanti, Paolo, Bellacosa, C., Calza, L., Abeli, C., Celesia, B. M., Grosso, C., Stagno, A., Mazzotta, F., Penco, G., Cassola, G., Nicolini, L. A., Dentone, C., Molteni, C., Palvarini, L., Scalzini, A., Carenzi, L., Rizzardini, G., Valsecchi, L., Cordier, L., Rusconi, S., Colombo, Valeria, Galli, M., Franzetti, M., Sgrelli, A., Mazzotta, E., Parruti, G., Bagella, P., Mura, M. S., Libertone, R., Antinori, A., Di Giambenedetto, S., Guastavigna, M., Caramello, P., Taramasso, L, Tatarelli, P, Ricci, E, Madeddu, G, Menzaghi, B, Squillace, N, De Socio, G, Martinelli, C, Gulminetti, R, Maggi, P, Orofino, G, Vichi, F, Di Biagio, A, Bonfanti, P, Bellacosa, C, Calza, L, Abeli, C, Celesia, B, Grosso, C, Stagno, A, Mazzotta, F, Penco, G, Cassola, G, Nicolini, L, Dentone, C, Molteni, C, Palvarini, L, Scalzini, A, Carenzi, L, Rizzardini, G, Valsecchi, L, Cordier, L, Rusconi, S, Colombo, V, Galli, M, Franzetti, M, Sgrelli, A, Mazzotta, E, Parruti, G, Bagella, P, Mura, M, Libertone, R, Antinori, A, Di Giambenedetto, S, Guastavigna, M, Caramello, P, Taramasso, L., Tatarelli, Paola, Ricci, Elena, Madeddu, G., Menzaghi, B., Squillace, Nicola, De Socio, G. V., Martinelli, C., Gulminetti, Roberto, Maggi, P., Orofino, G., Vichi, F., Di Biagio, A., Bonfanti, Paolo, Bellacosa, C., Calza, L., Abeli, C., Celesia, B. M., Grosso, C., Stagno, A., Mazzotta, F., Penco, G., Cassola, G., Nicolini, L. A., Dentone, C., Molteni, C., Palvarini, L., Scalzini, A., Carenzi, L., Rizzardini, G., Valsecchi, L., Cordier, L., Rusconi, S., Colombo, Valeria, Galli, M., Franzetti, M., Sgrelli, A., Mazzotta, E., Parruti, G., Bagella, P., Mura, M. S., Libertone, R., Antinori, A., Di Giambenedetto, S., Guastavigna, M., and Caramello, P.
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0301 basic medicine ,Cyclopropanes ,Male ,Protease Inhibitor ,Integrase inhibitor ,HIV Infections ,Gastroenterology ,Piperazines ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,HIV Infection ,030212 general & internal medicine ,medicine.diagnostic_test ,Elvitegravir ,Drug Substitution ,HIV-Associated Lipodystrophy Syndrome ,Lipid ,Middle Aged ,Lipids ,Infectious Diseases ,Cholesterol ,Treatment Outcome ,Rilpivirine ,Alkynes ,Dolutegravir ,Drug Therapy, Combination ,Female ,Heterocyclic Compounds, 3-Ring ,Cholesterol, Dyslipidemia,Framingham risk score, Integrase inhibitors, Rilpivirine ,Human ,medicine.drug ,Research Article ,Benzoxazine ,Adult ,medicine.medical_specialty ,Efavirenz ,Anti-HIV Agents ,Pyridones ,030106 microbiology ,Integrase Inhibitors ,Drug Administration Schedule ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Internal medicine ,Oxazines ,medicine ,Humans ,lcsh:RC109-216 ,Protease Inhibitors ,Ritonavir ,business.industry ,Anti-HIV Agent ,Lipid Metabolism ,Benzoxazines ,Integrase Inhibitor ,chemistry ,Dyslipidemia ,Framingham risk score ,Cohort Studie ,Lipid profile ,business - Abstract
Background: Dyslipidemia represents a significant non-infectious comorbidity among people living with HIV. The aim of this study is to evaluate the impact on lipid profile of switches from an efavirenz (EFV) or protease inhibitor/ritonavir (PI/r)-based regimen to a rilpivirine (RPV) or a once-daily integrase inhibitor-based regimen. Methods: We analyzed data from SCOLTA prospective database. All patients with HIV-RNA < 50 copies/ml in therapy with two NRTI + EFV or PI/r were included if they switched from EFV to dolutegravir (group EFV-DTG), elvitegravir (EFV-EVG), or RPV (EFV-RPV) and from PI/r to DTG (PI/r-DTG), PI/r to EVG (PI/r-EVG), or PI/r to RPV (PI/r-RPV). Total cholesterol (TC), TC/HDL ratio, LDL-cholesterol (LDL) and triglycerides (TG) were compared at baseline, six months and one year. Comparisons among groups were performed by a general linear model. Results: Four hundred and ninety patients were enrolled, 24.9% female, mean age 47.3 years (±10.1). According to ART switch, 11.4% were classified in group EFV-DTG, 3.9% in EFV-EVG, 23.9% in EFV-RPV, 17.6% in PI/r-DTG, 17.8% in PI/r-EVG, and 25.5% in PI/r-RPV. After adjusted analysis, TC significantly decreased in all groups but EFV-EVG, TC/HDL in all but EFV-DTG and EFV-EVG, while the reduction of TG was significant only in switches to RPV (EFV-RPV and PI/r-RPV). The one year decrease of TC, TC/HDL, LDL and TG was higher in patients with higher baseline levels of the same variable (p < .0001 for all). Conclusions: In SCOLTA, all switches from PI/r regimens gave advantages on lipid profile, while stopping EFV had consistently favorable lipid effects only if replaced by RPV.
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- 2018
116. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis
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Giada Carolo, Veronica Bernabucci, Luchino Chessa, Maria Luisa Russo, Giorgio Maria Saracco, Marzia Montalbano, Barbara Menzaghi, Giovanni Di Perri, Adriano Lazzarin, Silvia La Monica, Raffaele Bruno, Gian Ludovico Rapaccini, Mario U. Mondelli, Anna Maria Schimizzi, Caterina Pasquazzi, Maurizia Rossana Brunetto, Antonio Craxì, Filomena Morisco, Carmela Lo Guercio, Vania Giacomet, Alessia Giorgini, Mario Masarone, Francesca Paolo Russo, T. Zolfino, Vincenzo Sangiovanni, Alessia Ciancio, Antonella d'Arminio Monforte, Savino Bruno, E.M. Erne, Antonio Gasbarrini, Francesco Castelli, Sergio Novara, G. Nardone, Andrea De Luca, Claudio Maria Mastroianni, Gioacchino Angarano, Chiara Dentone, Renato Maserati, Anna Maria Piscaglia, Tiziana Quirino, Giuseppe Tarantino, M. Lichtner, Antonio Chirianni, Giuseppina Brancaccio, S. Paganin, Alfredo Alberti, Silvia Corradori, Edoardo G. Giannini, Carlo Torti, Chiara Boarini, Raffaele Cozzolongo, Marco Di Stefano, Alessandro Soria, Paolo Tundi, Giovanni Cassola, Debora Angrisani, Antonio Grieco, Cecilia Pravadelli, Giuliano Rizzardini, Roberto Gulminetti, Vincenzo Messina, Maria Rendina, Massimo Pirisi, Irene Cacciola, Roberto Ganga, Raffaella Lionetti, Paolo Calabrese, Laura Ponti, Filomena Simeone, Maurizio Russello, Monica Monti, Nicola Boffa, Pierluigi Tarquini, Franco Capra, Ivo Avancini, Domenico Sansonno, Stefano Fagiuoli, Michele Barone, Giacomo Vecchiet, Salvatore Rizzo, Carlo Federico Perno, Teresa Santantonio, Pierluigi Toniutto, Massimo Zuin, Nicola Caporaso, Alessandra Orlandini, Grazielle Marie Pigozzi, Martina Felder, Antonio Cristaudo, Roberto Cecere, Massimo Marignani, Vincenza Calvaruso, G. Abbati, Domenico Potenza, Maria Chiara Piras, Mario Rizzetto, Serena Cima, Marco delle Monache, Alessio Aghemo, D. Ieluzzi, Guglielmo Borgia, Giampaolo Corti, Paolo Poggio, Manuela Merli, Elena Danieli, Andrea Giacometti, Massimo Andreoni, Antonino Picciotto, Mario Angelico, Benedetta Canovari, Sara Piovesan, Anna Linda Zignego, Antonio Benedetti, Emanuele Durante, Erica Villa, Marcello Persico, Antonio Patrizio Termite, Barbara Coco, Maria Vinci, Lucio Boglione, Cristina Rossi, Paolo Angeli, Massimo Memoli, Maria Teresa Giordani, Massimo De Luca, Luisa Pasulo, Vincenzo Vullo, Mario Melazzini, Attilio Solinas, Pietro Gatti, Michele Guerra, Silvia Martini, Antonio Ascione, Massimo Puoti, Roberto Cauda, Giovanna Onnelli, Silvia Magnani, Salvatore Madonna, Giovanni Raimondo, Marco Tabone, Gloria Taliani, Dante Romagnoli, Aldo Marrone, Umberto Vespasiani Gentilucci, Luca Miele, Marcello Tavio, Andrea Antinori, Giampiero D'Offizi, Mirella Onofrio, Valentina Iodice, Lucio Cosco, Guido Piai, Luca Pani, Francesca Ceccherini Silberstein, Simona Montilla, Marco Lenzi, Luca Fontanella, Alessandro Federico, Carlo Ferrari, Giustino Parruti, Antonio Di Biagio, Gabriella Verucchi, Fabio Marsetti, Michele Milella, Maria Grazia Rumi, Antonio Izzi, Marco Marzioni, Francesca Donato, Vanni Borghi, Mariano Quartini, Massimo Colombo, Michele Imparato, Giovanni Battista Gaeta, P.L. Blanc, Alfredo Di Leo, Nicola Coppola, Alessandro Chiodera, Ivana Maida, Davide Campagnolo, Cinzia Antonini, Antonietta Romano, A. Gianstefani, Katia Falasca, Massimo Levrero, Gaetano Serviddio, Maria Paola Trotta, Olivia Morelli, Salvatore Petta, Elisabetta Teti, Maria Rita Parisi, Pietro Andreone, Ascione, Antonio, De Luca, Massimo, Melazzini, Mario, Montilla, Simona, Trotta, Maria Paola, Petta, Salvatore, Puoti, Massimo, Sangiovanni, Vincenzo, Messina, Vincenzo, Bruno, Savino, Izzi, Antonio, Villa, Erica, Aghemo, Alessio, Zignego, Anna Linda, Orlandini, Alessandra, Fontanella, Luca, Gasbarrini, Antonio, Marzioni, Marco, Giannini, Edoardo G., Craxì, Antonio, Abbati, Giuseppe, Alberti, Alfredo, Andreone, Pietro, Andreoni, Massimo, Angeli, Paolo, Angelico, Mario, Angarano, Gioacchino, Angrisani, Debora, Antinori, Andrea, Antonini, Cinzia, Avancini, Ivo, Barone, Michele, Bruno, Raffaele, Benedetti, Antonio, Bernabucci, Veronica, Blanc, Pier, Boarini, Chiara, Boffa, Nicola, Boglione, Lucio, Borghi, Vanni, Borgia, Guglielmo, Brancaccio, Giuseppina, Brunetto, Maurizia, Cacciola, Irene, Calabrese, Paolo, Calvaruso, Vincenza, Campagnolo, Davide, Canovari, Benedetta, Caporaso, Nicola, Capra, Franco, Carolo, Giada, Cassola, Giovanni, Castelli, Francesco, Cauda, Roberto, Silberstein, Francesca Ceccherini, Cecere, Roberto, Chessa, Luchino, Chiodera, Alessandro, Chirianni, Antonio, Ciancio, Alessia, Cima, Serena, Coco, Barbara, Colombo, Massimo, Coppola, Nicola, Corti, Giampaolo, Cosco, Lucio, Corradori, Silvia, Cozzolongo, Raffaele, Cristaudo, Antonio, Danieli, Elena, Monforte, Antonella D’Arminio, Monache, Marco delle, Del Poggio, Paolo, de Luca, Andrea, Dentone, Chiara, Di Biagio, Antonio, Di Leo, Alfredo, Di Perri, Giovanni, Di Stefano, Marco, D’Offizi, Giampiero, Donato, Francesca, Durante, Emanuele, Erne, Elke, Fagiuoli, Stefano, Falasca, Katia, Federico, Alessandro, Felder, Martina, Ferrari, Carlo, Gaeta, Giovanni Battista, Ganga, Roberto, Gatti, Pietro, Giacomet, Vania, Giacometti, Andrea, Gianstefani, Alice, Giordani, Maria, Giorgini, Alessia, Grieco, Antonio, Guerra, Michele, Gulminetti, Roberto, Ieluzzi, Donatella, Imparato, Michele, Iodice, Valentina, La Monica, Silvia, Lazzarin, Adriano, Lenzi, Marco, Levrero, Massimo, Lichtner, Myriam, Lionetti, Raffaella, Guercio, Carmela Lo, Madonna, Salvatore, Magnani, Silvia, Maida, Ivana, Marignani, Massimo, Marrone, Aldo, Marsetti, Fabio, Martini, Silvia, Masarone, Mario, Maserati, Renato, Mastroianni, Claudio Maria, Memoli, Massimo, Menzaghi, Barbara, Merli, Manuela, Miele, Luca, Milella, Michele, Mondelli, Mario, Montalbano, Marzia, Monti, Monica, Morelli, Olivia, Morisco, Filomena, Nardone, Gaetano, Novara, Sergio, Onnelli, Giovanna, Onofrio, Mirella, Paganin, Simona, Pani, Luca, Parisi, Maria Rita, Parruti, Giustino, Pasquazzi, Caterina, Pasulo, Luisa, Perno, Carlo Federico, Persico, Marcello, Piai, Guido, Picciotto, Antonino, Pigozzi, Grazielle Marie, Piovesan, Sara, Piras, Maria Chiara, Pirisi, Massimo, Piscaglia, Anna Maria, Ponti, Laura, Potenza, Domenico, Pravadelli, Cecilia, Quartini, Mariano, Quirino, Tiziana, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Rendina, Maria, Rizzardini, Giuliano, Rizzetto, Mario, Rizzo, Salvatore, Romagnoli, Dante, Romano, Antonietta, Rossi, Cristina, Rumi, Maria Grazia, Russello, Maurizio, Russo, Francesca Paolo, Russo, Maria Luisa, Sansonno, Domenico Ettore, Santantonio, Teresa Antonia, Saracco, Giorgio, Schimizzi, Anna Maria, Serviddio, Gaetano, Simeone, Filomena, Solinas, Attilio, Soria, Alessandro, Tabone, Marco, Taliani, Gloria, Tarantino, Giuseppe, Tarquini, Pierluigi, Tavio, Marcello, Termite, Antonio, Teti, Elisabetta, Toniutto, Pierluigi, Torti, Carlo, Tundi, Paolo, Vecchiet, Giacomo, Verucchi, Gabriella, Gentilucci, Umberto Vespasiani, Vinci, Maria, Vullo, Vincenzo, Zolfino, Teresa, Zuin, Massimo, Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, and Zuin, M
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Cyclopropanes ,Liver Cirrhosis ,Male ,Cirrhosis ,Dasabuvir ,Elderly ,Ombitasvir ,Paritaprevir ,Aged ,80 and over ,Anilides ,Antiviral Agents ,Biomarkers ,Carbamates ,Female ,Hepacivirus ,Hepatitis C ,Chronic ,Humans ,Macrocyclic Compounds ,Ribavirin ,Ritonavir ,Sulfonamides ,Treatment Outcome ,Uracil ,Drug Therapy ,Combination ,Genotype ,Cirrhosis, Dasabuvir, Elderly, Ombitasvir, Paritaprevir, Microbiology (medical), Infectious Diseases ,Aged, 80 and over ,Hepatitis C, Chronic ,Drug Therapy, Combination ,Microbiology (medical) ,Infectious Diseases ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,2-Naphthylamine ,Medicine ,030212 general & internal medicine ,Valine ,General Medicine ,030211 gastroenterology & hepatology ,Macrocyclic Compound ,medicine.drug ,Human ,medicine.medical_specialty ,Proline ,Lactams, Macrocyclic ,Settore MED/12 - GASTROENTEROLOGIA ,Liver Cirrhosi ,Sulfonamide ,03 medical and health sciences ,Internal medicine ,Decompensation ,Hepatitis ,Antiviral Agent ,Cirrhosi ,Hepaciviru ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Anilide ,Biomarker ,medicine.disease ,chemistry ,Carbamate ,business - Abstract
Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.
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- 2018
117. Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy
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Bertoli, Ada, Sorbo, Maria Chiara, Aragri, Marianna, Lenci, Ilaria, Teti, Elisabetta, Polilli, Ennio, Di Maio, Velia Chiara, Gianserra, Laura, Biliotti, Elisa, Masetti, Chiara, Magni, Carlo F., Babudieri, Sergio, Nicolini, Laura A., Milana, Martina, Cacciatore, Pierluigi, Sarmati, Loredana, Pellicelli, Adriano, Paolucci, Stefania, Craxì, Antonio, Morisco, Filomena, Palitti, Valeria Pace, Siciliano, Massimo, Coppola, Nicola, Iapadre, Nerio, Puoti, Massimo, Rizzardini, Giuliano, Taliani, Gloria, Pasquazzi, Caterina, Andreoni, Massimo, Parruti, Giustino, Angelico, Mario, Perno, Carlo Federico, Cento, Valeria, Ceccherini-Silberstein, Francesca, Andreone, Pietro, Baldanti, Fausto, Barbarini, Giorgio, Boccaccio, Vincenzo, Boglione, Lucio, Bolis, Matteo, Bonora, Stefano, Borghi, Vanni, Brancaccio, Giuseppina, Bruno, Savino, Bruzzone, Bianca, Calvaruso, Vincenza, Caporaso, Nicola, Ciaccio, Antonio, Ciancio, Alessia, Colombatto, Piero, Cozzolongo, Raffaele, D'Ambrosio, Cecilia, D'Ettorre, Gabriella, De Leonardis, Francesco, De Luca, Andrea, Di Biagio, Antonio, Di Perri, Giovanni, Francioso, Simona, Gaeta, Giovanni Battista, Gasbarrini, Antonio, Ghisetti, Valeria, Giorgini, Alessia, Grieco, Antonio, Gubertini, Guido, Gulminetti, Roberto, Lambiase, Lara, Landonio, Simona, Lichtner, Miriam, Maida, Ivana, Marenco, Simona, Marinaro, Letizia, Maserati, Renato, Melis, Michela, Menzaghi, Barbara, Meregalli, Elisa, Micheli, Valeria, Niero, Fosca, Paoloni, Maurizio, Pieri, Alessandro, Rendina, Maria, Romagnoli, Dante, Rossetti, Barbara, Ruggiero, Tina, Sangiovanni, Vincenzo, Starace, Mario, Sticchi, Laura, Tarquini, Pierluigi, Toniutto, Pierluigi, Vullo, Vincenzo, Zazzi, Maurizio, HCV Virology Italian Resistance Network, Bertoli A1, Sorbo MC1, Aragri M1, Lenci I2, Teti E3, Polilli E4, Di Maio VC1, Gianserra L5, Biliotti E6, Masetti C2, Magni CF7, Babudieri S8, Nicolini LA9, Milana M2, Cacciatore P4, Sarmati L3, Pellicelli A10, Paolucci S11, Craxì A, Morisco F13, Palitti VP14, Siciliano M15, Coppola N16, Iapadre N17, Puoti M18, Rizzardini G7, Taliani G6, Pasquazzi C5, Andreoni M3, Parruti G4, Angelico M2, Perno CF19, Cento V20, Ceccherini-Silberstein F1, HCV Virology Italian Resistance Network (VIRONET-C)., Bertoli, Ada, Sorbo, Maria Chiara, Aragri, Marianna, Lenci, Ilaria, Teti, Elisabetta, Polilli, Ennio, Di Maio, Velia Chiara, Gianserra, Laura, Biliotti, Elisa, Masetti, Chiara, Magni, Carlo F., Babudieri, Sergio, Nicolini, Laura A., Milana, Martina, Cacciatore, Pierluigi, Sarmati, Loredana, Pellicelli, Adriano, Paolucci, Stefania, Craxì, Antonio, Morisco, Filomena, Palitti, Valeria Pace, Siciliano, Massimo, Coppola, Nicola, Iapadre, Nerio, Puoti, Massimo, Rizzardini, Giuliano, Taliani, Gloria, Pasquazzi, Caterina, Andreoni, Massimo, Parruti, Giustino, Angelico, Mario, Perno, Carlo Federico, Cento, Valeria, Ceccherini-Silberstein, Francesca, Andreone, Pietro, Baldanti, Fausto, Barbarini, Giorgio, Boccaccio, Vincenzo, Boglione, Lucio, Bolis, Matteo, Bonora, Stefano, Borghi, Vanni, Brancaccio, Giuseppina, Bruno, Savino, Bruzzone, Bianca, Calvaruso, Vincenza, Caporaso, Nicola, Ciaccio, Antonio, Ciancio, Alessia, Colombatto, Piero, Cozzolongo, Raffaele, D'Ambrosio, Cecilia, D'Ettorre, Gabriella, De Leonardis, Francesco, De Luca, Andrea, Di Biagio, Antonio, Di Perri, Giovanni, Francioso, Simona, Gaeta, Giovanni Battista, Gasbarrini, Antonio, Ghisetti, Valeria, Giorgini, Alessia, Grieco, Antonio, Gubertini, Guido, Gulminetti, Roberto, Lambiase, Lara, Landonio, Simona, Lichtner, Miriam, Maida, Ivana, Marenco, Simona, Marinaro, Letizia, Maserati, Renato, Melis, Michela, Menzaghi, Barbara, Meregalli, Elisa, Micheli, Valeria, Niero, Fosca, Paoloni, Maurizio, Pieri, Alessandro, Rendina, Maria, Romagnoli, Dante, Rossetti, Barbara, Ruggiero, Tina, Sangiovanni, Vincenzo, Starace, Mario, Sticchi, Laura, Tarquini, Pierluigi, Toniutto, Pierluigi, Vullo, Vincenzo, Zazzi, Maurizio, 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, Sorbo, Mc, Di Maio, Vc, Magni, Cf, Nicolini, La, Craxì, A, Palitti, Vp, Perno, Cf, Gaeta, Gb, and Zazzi, M.
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Male ,0301 basic medicine ,Sofosbuvir ,Hepacivirus ,Drug Resistance ,lcsh:Medicine ,Viral Nonstructural Proteins ,medicine.disease_cause ,Gastroenterology ,Hepatitis C Virus ,HCV resistance-test ,chemistry.chemical_compound ,0302 clinical medicine ,Genotype ,Prevalence ,Viral ,lcsh:Science ,Multidisciplinary ,biology ,Hepatitis C ,Middle Aged ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Italy ,Cohort ,HCV ,Female ,030211 gastroenterology & hepatology ,medicine.drug ,Adult ,medicine.medical_specialty ,HCV RAS ,Hepatitis C virus ,03 medical and health sciences ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Aged ,NS5A ,NS5B ,business.industry ,lcsh:R ,Hepatitis C Virus, HCV resistance-test ,biology.organism_classification ,medicine.disease ,030104 developmental biology ,chemistry ,lcsh:Q ,business - 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.
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- 2018
118. Resistance test guided retreatment of HCV infected patients with a previous failure to a NS5A inhibitor-containing regimen: the Italian Vironet C real life experience
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Pietro Lampertico, Valeria Cento, Claudio Maria Mastroianni, M. Puoti, Giuliano Rizzardini, Maurizio Zazzi, M. Lichtner, Bianca Bruzzone, Ivana Maida, Elisabetta Degasperi, C.F. Perno, M. Rendina, Giustino Parruti, Vincenza Calvaruso, Gloria Taliani, F. Di Lorenzo, Ilaria Lenci, Anna Claudia Pellicelli, Caterina Pasquazzi, Stefania Paolucci, A. Raddi, Marianna Aragri, Ennio Polilli, Giulia Morsica, Mario Starace, M. Andreoni, M. Di Stefano, C. Minichini, L. Donnarumma, V. Guarneri, Simona Marenco, Simona Landonio, Raffaele Cozzolongo, V. Pace Palitti, N. Cuomo, P. Andreone, Nicola Coppola, Silvia Galli, Mario Angelico, C. Paternoster, Roberto Ganga, Vanni Borghi, Elisabetta Teti, Sergio Babudieri, Silvia Barbaliscia, Anna Licata, Giovanni Cenderello, Antonio Craxì, Filomena Morisco, Maurizia Rossana Brunetto, V.C. Di Maio, Vincenzo Sangiovanni, A. Ciancio, Piero Colombatto, Valeria Micheli, Teresa Pollicino, Laura Ambra Nicolini, Alessia Giorgini, Valeria Ghisetti, S. Novati, Annapaola Callegaro, Aldo Bertoli, E. Milano, Roberto Gulminetti, A. De Santis, F. Ceccherini-Silberstein, Teresa Santantonio, C. Masetti, G. Raimondo, Di Maio, V.C., Aragri, M., Masetti, C., Paolucci, S., Bruzzone, B., Degasperi, E., Barbaliscia, S., Pollicino, T., Minichini, C., Calvaruso, V., Rendina, M., Cento, V., Teti, E., Micheli, V., Ghisetti, V., Polilli, E., Palitti, V. Pace, Landonio, S., Lenci, I., Donnarumma, L., Nicolini, L.A., Bertoli, A., Starace, M., Pasquazzi, C., Callegaro, A.P., Morisco, F., Cenderello, G., Marenco, S., Gulminetti, R., Novati, S., Guarneri, V., Andreone, P., Galli, S., Ciancio, A., Sangiovanni, V., Cuomo, N., Raddi, A., Morsica, G., Borghi, V., Maida, I., Brunetto, M., Colombatto, P., Cozzolongo, R., De Santis, A., Lichtner, M., Babudieri, S., Taliani, G., Santantonio, T., Di Stefano, M., Paternoster, C., Ganga, R., Puoti, M., Rizzardini, G., Pellicelli, A., Milano, E., Mastroianni, C., Licata, A., Di Lorenzo, F., Giorgini, A., Lampertico, P., Parruti, G., Coppola, N., Zazzi, M., Raimondo, G., Andreoni, M., Craxì, A., Angelico, M., Perno, C.F., and Ceccherini-Silberstein, F.
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Resistance test ,medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,DAA failur ,Vironet C ,NS5A ,Regimen ,Internal medicine ,medicine ,retreatment ,business - Abstract
Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/131/20), grazoprevir/elbasvir ± ribavirin (N = 34), glecaprevir/pibrentasvir (N = 20). Notably, 18.1% of NS5A-failing patients did not show any resistance-associated-substitutions (RAS), while 81.9% showed at least one NS5A-RAS, with multiclass-resistance in 35.5%. NS5A-RAS were observed more frequently in glecaprevir/pibrentasvir failures (GT1a 83.3%: Y93H + Q30H/D or +H58D; GT3a: 83.3% Y93H + A30K/G or +L31I) compared to sofosbuvir/velpatasvir (GT1a 16.6%: Y93H + Q30H, p = 0.08; GT3a 20.0%: Y93H/N + A30K/T, p = 0.03). To date, 105 failures have started a retreatment: sofosbuvir/velpatasvir ± ribavirin (N = 30), sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (N = 67), glecaprevir/pibrentasvir (N = 4), grazoprevir/elbasvir ± sofosbuvir + ribavirin (N = 3), 3D + sofosbuvir + ribavirin (N = 1). The majority of patients were cirrhotic (51.9%) and relapsers (87.5%). The prevalence of NS5A-RASs before retreatment was 80.9%, with multiclass-resistance 29.5%. Among patients completing post-retreatment follow-up, a sustained-viral-response at week 12 (SVR12) was observed in 26/33 (78.8%). SVR4 was documented in 49/56 (87.5%). SVR12 was 76.0% with sofosbuvir/velpatasvir ± ribavirin (N = 25). Differently, SVR12 was 100% with glecaprevir/pibrentasvir for 8/12/16 weeks (N = 3), grazoprevir/elbasvir ± sofosbuvir + ribavirin for 12/24 weeks (N = 3) or 3D + sofosbuvir + ribavirin for 24 weeks (N = 1), despite the presence of NS5A-RASs. Until now, 67 patients started sofosbuvir/velpatasvir/voxilaprevir ± ribavirin recommended-retreatment for 12 weeks. 54/67 (80.6%) showed at least one baseline NS5A-RAS, 23/67 (34.3%) multiple-NS5A-RASs, and 22/67 (32.8%) multiclass-resistance. Of 25 patients with available outcome, 96.0% had SVR4. Only 1 GT1b infected patient was non-responder, without RASs before retreatment. Conclusions: In this real-life setting, NS5A-RASs were frequently detected at failure, and multiclass-resistance was around 30%. Overall, SVR after resistance-test-guided retreatment was >95%, with the exception of the sofosbuvir/velpatasvir retreatment. Our results show how HCV resistance-test at failure may be useful to optimize retreatment strategies.
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- 2019
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119. Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study
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Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, ASCIONE, ANTONIO, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxì, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, BARONE, MICHELE, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, de Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Ludovico Rapaccini, Gian, Miele, Luca, Cima, Serena, Luisa Russo, Maria, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, NARDONE, GERARDO ANTONIO PIO, Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, Ascione, Antonio, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxì, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, Barone, Michele, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, de Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Ludovico Rapaccini, Gian, Miele, Luca, Cima, Serena, Luisa Russo, Maria, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, Petta, S., Marzioni, M., Russo, P., Aghemo, A., Alberti, A., Ascione, A., Antinori, A., Bruno, R., Bruno, S., Chirianni, A., Gaeta, G., Giannini, E., Merli, M., Messina, V., Montilla, S., Perno, C., Puoti, M., Raimondo, G., Rendina, M., Silberstein, F., Villa, E., Zignego, A., Pani, L., Craxi, A., Tabone, M., Andreoni, M., Teti, E., Angelico, M., Persico, M., Masarone, M., Chiodera, A., Solinas, A., delle Monache, M., Cecere, R., Maria Schimizzi, A., Piovesan, S., Campagnolo, D., Chiara Piras, M., Zolfino, T., Paolo Russo, F., Morelli, O., Sangiovanni, V., Onofrio, M., Iodice, V., Izzi, A., Pirisi, M., Danieli, E., Vinci, M., Rizzardini, G., Fagiuoli, S., Pasulo, L., D'Arminio Monforte, A., Zuin, M., Giorgini, A., Simeone, F., Piali, G., Lo Guercio, C., Federico, A., Brancaccio, G., Marrone, A., Abbati, G., Boarini, C., Borghi, V., Bernabucci, V., Corti, G., Monti, M., Rizzetto, M., Martini, S., Andreone, P., Gianstefani, A., Lenzi, M., Verucchi, G., Toniutto, P., Borgia, G., Caporaso, N., Morisco, F., Nardone, G., Angrisani, D., Giacometti, A., Benedetti, A., Tarantino, G., Marsetti, F., Tavio, M., Novara, S., Antonia Santantonio, T., Serviddio, G., Brunetto, M., Coco, B., Angarano, G., Milella, M., Barone, M., Di Leo, A., Ettore Sansonno, D., Cacciola, I., Boffa, N., Saracco, G., Di Biagio, A., Picciotto, A., de Luca, A., Calvaruso, V., Corradori, S., Ferrari, C., Orlandini, A., Maida, I., Torti, C., Chessa, L., Felder, M., Vespasiani Gentilucci, U., Angeli, P., Romano, A., Ludovico Rapaccini, G., Miele, L., Cima, S., Luisa Russo, M., Cozzolongo, R., Onnelli, G., D'Offizi, G., Lionetti, R., Montalbano, M., Guerra, M., Di Perri, G., Boglione, L., Capra, F., Carolo, G., Ieluzzi, D., Antonini, C., Termite, A., Madonia, S., Tarquini, P., Parruti, G., Vecchiet, G., Falasca, K., Menzaghi, B., Quirino, T., Dentone, C., Maria Piscaglia, A., Rossi, C., Giordani, M., Fontanella, L., Cassola, G., Russello, M., Cristaudo, A., Giacomet, V., Colombo, M., Donato, F., Durante, E., Cosco, L., Marignani, M., Quartini, M., Memoli, M., Ganga, R., Ponti, L., Soria, A., Grazia Rumi, M., Gulminetti, R., Maserati, R., Mondelli, M., Lazzarin, A., Rita Parisi, M., Canovari, B., Avancini, I., Pravadelli, C., Blanc, P., Pasquazzi, C., Maria Mastroianni, C., Lichtner, M., Distefano, M., Magnani, S., Paganin, S., Erne, E., Gatti, P., Tundi, P., Calabrese, P., Gasbarrini, A., Grieco, A., Coppola, N., Del Poggio, P., Levrero, M., Talliani, G., Vullo, V., Cauda, R., La Monica, S., Potenza, D., Rizzo, S., Castelli, F., Marie Pigozzi, G., Ciancio, A., Romagnoli, D., Barchetti, F., Ivanovic, J., Longo, O., Petraglia, S., Paola Trotta, M., Savino, Bruno, Nardone, GERARDO ANTONIO PIO, Petta, S, Marzioni, M, Russo, P, Aghemo, A, Alberti, A, Ascione, A, Antinori, A, Bruno, R, Bruno, S, Chirianni, A, Gaeta, G, Giannini, E, Merli, M, Messina, V, Montilla, S, Perno, C, Puoti, M, Raimondo, G, Rendina, M, Silberstein, F, Villa, E, Zignego, A, Pani, L, Craxì, A, and Fagiuoli, S
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Cyclopropanes ,Compassionate Use Trials ,Liver Cirrhosis ,Male ,chemistry.chemical_compound ,0302 clinical medicine ,2-Naphthylamine ,HCV, direct-acting antiviral, mixed cryoglobulinemia, RBV ,Anilides ,030212 general & internal medicine ,Longitudinal Studies ,Prospective Studies ,Chronic ,Adult ,Aged ,Antiviral Agents ,Carbamates ,Drug Therapy, Combination ,Female ,Genotype ,Hepatitis C, Chronic ,Humans ,Macrocyclic Compounds ,Middle Aged ,Ribavirin ,Ritonavir ,Sulfonamides ,Treatment Outcome ,Uracil ,Settore MED/12 - Gastroenterologia ,Dasabuvir ,HCV DAA ,Gastroenterology ,virus diseases ,Valine ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Hepatitis C ,Hepatology ,Combination ,030211 gastroenterology & hepatology ,medicine.drug ,medicine.medical_specialty ,Proline ,Lactams, Macrocyclic ,Hepatitis C virus genotype 1, Hepatitis C virus genotype 4, decompensated liver cirrhosis, antiviral therapy, dasabuvir, ombitasvir, paritaprevir ,03 medical and health sciences ,Drug Therapy ,Internal medicine ,medicine ,Decompensation ,Adverse effect ,business.industry ,Virology ,Ombitasvir ,Clinical trial ,chemistry ,Paritaprevir ,business - Abstract
Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Findings 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83–12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. Interpretation Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practice. Funding Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di Palermo.
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- 2017
120. Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study
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Kondili, Loreta A., GAETA, Giovanni Battista, Ieluzzi, Donatella, Zignego, Anna Linda, Monti, Monica, Gori, Andrea, Soria, Alessandro, Raimondo, Giovanni, Filomia, Roberto, Leo, Alfredo Di, Iannone, Andrea, Massari, Marco, Corsini, Romina, Gulminetti, Roberto, Comini, Alberto Gatti, Toniutto, Pierluigi, Dissegna, Denis, Russo, Francesco Paolo, Zanetto, Alberto, Rumi, Maria Grazia, Brancaccio, Giuseppina, Danieli, Elena, Brunetto, Maurizia Rossana, Weimer, Liliana Elena, Quaranta, Maria Giovanna, Vella, Stefano, Puoti, Massimo, PITER Cohort Study, FEDERICO, Alessandro, Dallio, M, LOGUERCIO, Carmelina, Kondili, L, Gaeta, G, Ieluzzi, D, Zignego, A, Monti, M, Gori, A, Soria, A, Raimondo, G, Filomia, R, Leo, A, Iannone, A, Massari, M, Corsini, R, Gulminetti, R, Comini, A, Toniutto, P, Dissegna, D, Russo, F, Zanetto, A, Rumi, M, Brancaccio, G, Danieli, E, Brunetto, M, Weimer, L, Quaranta, M, Vella, S, Puoti, M, Kondili, Loreta A., Gaeta, Giovanni Battista, Ieluzzi, Donatella, Zignego, Anna Linda, Monti, Monica, Gori, Andrea, Soria, Alessandro, Raimondo, Giovanni, Filomia, Roberto, Leo, Alfredo Di, Iannone, Andrea, Massari, Marco, Corsini, Romina, Gulminetti, Roberto, Comini, Alberto Gatti, Toniutto, Pierluigi, Dissegna, Deni, Russo, Francesco Paolo, Zanetto, Alberto, Rumi, Maria Grazia, Brancaccio, Giuseppina, Danieli, Elena, Brunetto, Maurizia Rossana, Weimer, Liliana Elena, Quaranta, Maria Giovanna, Vella, Stefano, Puoti, Massimo, PITER Cohort, Study, Federico, Alessandro, Dallio, M, and Loguercio, Carmelina
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Genetics and Molecular Biology (all) ,Male ,Cirrhosis ,Disease ,Hepacivirus ,Toxicology ,Biochemistry ,Viral infection ,0302 clinical medicine ,80 and over ,Medicine ,Prospective Studies ,Chronic ,lcsh:Science ,media_common ,Aged, 80 and over ,Liver Diseases ,Drug Interaction ,Italy ,Adult ,Aged ,Antiviral Agents ,Drug Administration Schedule ,Drug Therapy, Combination ,Female ,Hepatitis C, Chronic ,Humans ,Interferons ,Liver Cirrhosis ,Middle Aged ,Risk ,Drug Interactions ,Medicine (all) ,Biochemistry, Genetics and Molecular Biology (all) ,Agricultural and Biological Sciences (all) ,030220 oncology & carcinogenesis ,Interferon ,030211 gastroenterology & hepatology ,Human ,Cohort study ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Drug-Drug Interactions ,Gastroenterology and Hepatology ,Microbiology ,03 medical and health sciences ,Drug Therapy ,Pharmacology ,Hepaciviru ,Flaviviruses ,lcsh:R ,Organisms ,Correction ,medicine.disease ,Prospective Studie ,Regimen ,Immunology ,lcsh:Q ,RNA viruses ,lcsh:Medicine ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Cohort Studies ,Liver disease ,Drug Metabolism ,Medicine and Health Sciences ,030212 general & internal medicine ,Prospective cohort study ,Pathology and laboratory medicine ,Multidisciplinary ,HCV DAA ,Hepatitis C virus ,Antiviral therapy ,Medical microbiology ,Hepatitis C ,Real life data ,Research Design ,Combination ,Viruses ,Pathogens ,Research Article ,Liver Cirrhosi ,Biology ,Research and Analysis Methods ,Chronic hepatitis ,Internal medicine ,Pharmacokinetics ,In patient ,Antiviral Agent ,Biology and life sciences ,Toxicity ,business.industry ,Interferon free ,Viral pathogens ,Hepatitis viruses ,Microbial pathogens ,business - Abstract
Background There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. Aim To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. Methods Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org). Results Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. Conclusions Based on these results, we can estimate that 30–44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from “dose adjustment/closer monitoring”, in mild to moderate liver disease, to “the use is contraindicated” in severe liver disease.
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- 2018
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121. Performance of genotypic tropism testing on proviral DNA in clinical practice: Results from the DIVA study group
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Svicher, Valentina, Alteri, Claudia, Montano, Marco, D Arrigo, Roberta, Andreoni, Massimo, Angarano, Gioacchino, Antinori, Andrea, Antonelli, Guido, Allice, Tiziano, Bagnarelli, Patrizia, Baldanti, Fausto, Bertoli, Ada, Borderi, Marco, Boeri, Enzo, Bon, Isabella, Bruzzone, Bianca, Callegaro, Anna Paola, Capobianchi, Maria Rosaria, Carosi, Giampiero, Cauda, Roberto, Ceccherini-Silberstein, Francesca, Clementi, Massimo, Chirianni, Antonio, Manuela Colafigli, Monforte, Antonella D. Arminio, Luca, Andrea, Di Biagio, Antonio, Di Nicuolo, Giuseppe, Di Perri, Giovanni, Di Pietro, Massimo, Di Santo, Fabiola, Fabeni, Lavinia, Fadda, Giovanni, Galli, Massimo, Gennari, William, Ghisetti, Valeria, Giacometti, Andrea, Gori, Caterina, Gori, Andrea, Gulminetti, Roberto, Leoncini, Francesco, Maffongelli, Gaetano, Maggiolo, Franco, Manca, Giuseppe, Gargiulo, Franco, Martinelli, Canio, Maserati, Renato, Mazzotta, Francesco, Meini, Genny, Micheli, Valeria, Monno, Laura, Mussini, Cristina, Narciso, Pasquale, Nozza, Silvia, Paolucci, Stefania, Palu, Giorgio, Parisi, Saverio, Parruti, Giustino, Pignataro, Angela Rosa, Pollicita, Michela, Quirino, Tiziana, Re, Maria Carla, Rizzardini, Giuliano, Santangelo, Rosaria, Scaggiante, Renzo, Sterrantino, Gaetana, Turriziani, Ombretta, Vatteroni, Maria Linda, Vecchi, Laura, Viscoli, Claudio, Vullo, Vincenzo, Zazzi, Maurizio, Lazzarin, Adriano, Perno, Carlo Federico, Diva, Grp, Svicher V, Alteri C, Montano M, D'Arrigo R, Andreoni M, Angarano G, Antinori A, Antonelli G, Allice T, Bagnarelli P, Baldanti F, Bertoli A, Borderi M, Boeri E, Bon I, Bruzzone B, Callegaro AP, Capobianchi MR, Carosi G, Cauda R, Ceccherini-Silberstein F, Clementi M, Chirianni A, Colafigli M, D'Arminio Monforte A, De Luca A, Di Biagio A, Di Nicuolo G, Di Perri G, Di Pietro M, Di Santo F, Fabeni L, Fadda G, Galli M, Gennari W, Ghisetti V, Giacometti A, Gori C, Gori A, Gulminetti R, Leoncini F, Maffongelli G, Maggiolo F, Manca G, Gargiulo F, Martinelli C, Maserati R, Mazzotta F, Meini G, Micheli V, Monno L, Mussini C, Narciso P, Nozza S, Paolucci S, Pal G, Parisi S, Parruti G, Pignataro AR, Pollicita M, Quirino T, Re MC, Rizzardini G, Santangelo R, Scaggiante R, Sterrantino G, Turriziani O, Vatteroni ML, Vecchi L, Viscoli C, Vullo V, Zazzi M, Lazzarini A, Perno CF., Svicher, V, Alteri, C, Montano, M, D'Arrigo, R, Andreoni, M, Angarano, G, Antinori, A, Antonelli, G, Allice, T, Bagnarelli, P, Baldanti, F, Bertoli, A, Borderi, M, Boeri, E, Bon, I, Bruzzone, B, Callegaro, Ap, Capobianchi, Mr, Carosi, G, Cauda, R, Ceccherini Silberstein, F, Clementi, Massimo, Chirianni, A, Colafigli, M, Monforte, Ad, De Luca, A, Di Biagio, A, Di Nicuolo, G, Di Perri, G, Di Pietro, M, Di Santo, F, Fabeni, L, Fadda, G, Galli, M, Gennari, W, Ghisetti, V, Giacometti, A, Gori, C, Gori, A, Gulminetti, R, Leoncini, F, Maffongelli, G, Maggiolo, F, Manca, G, Gargiulo, F, Martinelli, C, Maserati, R, Mazzotta, F, Meini, G, Micheli, V, Monno, L, Mussini, C, Narciso, P, Nozza, S, Paolucci, S, Palu, G, Parisi, S, Parruti, G, Pignataro, Ar, Pollicita, M, Quirino, T, Re, Mc, Rizzardini, G, Santangelo, R, Scaggiante, R, Sterrantino, G, Turriziani, O, Vatteroni, Ml, Vecchi, L, Viscoli, C, Vullo, V, Zazzi, M, Lazzarin, Adriano, Perno, Cf, Callegaro, A, Capobianchi, M, Clementi, M, D'Arminio Monforte, A, Pal, G, Pignataro, A, Re, M, Vatteroni, M, Lazzarini, A, and Perno, C
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Male ,Genotype ,Genotyping Techniques ,IMPACT ,Mononuclear ,HIV-1 TROPISM ,Proviral DNA ,Reproducibility of Result ,HIV Infections ,CORECEPTOR SWITCH ,HIV Envelope Protein gp120 ,FREQUENCY ,Tropism ,CXCR4-USING HIV ,HIV ,AIDS ,DNA provirale ,ANTIRETROVIRAL THERAPY ,Proviruses ,INFECTION ,Leukocytes ,Humans ,HIV Infection ,CD4 CELL COUNT ,PLASMA RNA ,MARAVIROC ,Proviruse ,hiv ,tropism ,proviral dna ,virus diseases ,Reproducibility of Results ,Viral Load ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Viral Tropism ,HIV-1 ,Leukocytes, Mononuclear ,Female ,Genotyping Technique ,Human - Abstract
"Objective: The DIVA study is aimed at setting up a standardized genotypic tropism-testing on proviral-DNA for the routine clinical diagnostic-laboratory Methods: Twelve local centres and 5 reference centres (previously cross-validated) were identified. For inter-center validation-procedure, 60 peripheral-blood mononuclear cells (PBMCs) aliquots from 45 HAART-treated patients were randomly chosen for population V3 sequencing on proviral-DNA at local HIV centre and at reference-laboratory Viral tropism was predicted by Geno2Pheno algorithm (False Positive Rate [FPR] = 20%) as proposed by the European-Guidelines. Quantification of total HIV-1 DNA was based on a method described by Viard (2004). Results: Quantification of HIV-1 DNA was available for 35\/45 (77.8%) samples, and gave a median value of 598 (IQR:252-1,203) copies\/10(6) PBMCs. A total of 56\/60 (93.3%) samples were successfully amplified by both the reference and the local virological centers. The overall concordance of tropism prediction between local and reference centers was 54\/56 (96.4%). Results of tropism prediction by local centers were: 33\/54 (61.1%) R5 and 21\/54 (38.9%) X4\/DM. Conclusion: There was high concordance in the genotypic tropism prediction based on proviral DNA among different virological centers throughout Italy. Our results are in line with other European studies, and support the use of genotypic tropism testing on proviral DNA in patients with suppressed plasma HIV-1 RNA candidate to CCR5-antagonist treatment."
122. Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience
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Antonio Ascione, null CLEO Study Group, Luigi Elio Adinolfi, Pietro Amoroso, Angelo Andriulli, Orlando Armignacco, Tiziana Ascione, Sergio Babudieri, Giorgio Barbarini, Michele Brogna, Francesco Cesario, Vincenzo Citro, Ernesto Claar, Raffaele Cozzolongo, Giuseppe D’Adamo, Emilio D’Amico, Pellegrino Dattolo, Massimo De Luca, Vincenzo De Maria, Massimo De Siena, Giuseppe De Vita, Antonio Di Giacomo, Rosanna De Marco, Giorgio De Stefano, Giulio De Stefano, Sebastiano Di Salvo, Raffaele Di Sarno, Nunzia Farella, Laura Felicioni, Basilio Fimiani, Luca Fontanella, Giuseppe Foti, Caterina Furlan, Francesca Giancotti, Giancarlo Giolitto, Tiziana Gravina, Barbara Guerrera, Roberto Gulminetti, Angelo Iacobellis, Michele Imparato, Angelo Iodice, Vincenzo Iovinella, Antonio Izzi, Alfonso Liberti, Pietro Leo, Gennaro Lettieri, Ileana Luppino, Aldo Marrone, Ettore Mazzoni, Vincenzo Messina, Roberto Monarca, Vincenzo Narciso, Lorenzo Nosotti, Adriano Maria Pellicelli, Alessandro Perrella, Guido Piai, Antonio Picardi, Paola Pierri, Grazia Pietromatera, Francesco Resta, Luca Rinaldi, Mario Romano, Angelo Rossini, Maurizio Russello, Grazia Russo, Rodolfo Sacco, Vincenzo Sangiovanni, Antonio Schiano, Antonio Sciambra, Gaetano Scifo, Filomena Simeone, Annarita Sullo, Pierluigi Tarquini, Paolo Tundo, Alfredo Vallone, Ascione, A, Adinolfi, Luigi Elio, Amoroso, P, Andriulli, A, Armignacco, O, Ascione, T, Babudieri, S, Barbarini, G, Brogna, M, Cesario, F, Citro, V, Claar, E, Cozzolongo, R, D'Adamo, G, D'Amico, E, Dattolo, P, De Luca, M, De Maria, V, De Siena, M, De Vita, G, Di Giacomo, A, De Marco, R, De Stefano, G, Di Salvo, S, Di Sarno, R, Farella, N, Felicioni, L, Fimiani, B, Fontanella, L, Foti, G, Furlan, C, Giancotti, F, Giolitto, G, Gravina, T, Guerrera, B, Gulminetti, R, Iacobellis, A, Imparato, M, Iodice, A, Iovinella, V, Izzi, A, Liberti, 1, Leo, P, Lettieri, G, Luppino, I, Marrone, Aldo, Mazzoni, E, Messina, V1, Monarca, R, Narciso, V, Nosotti, L, Pellicelli, Am, Perrella, A, Piai, G, Picardi, A, Pierri, P, Pietromatera, G, Resta, F, Rinaldi, L, Romano, M, Rossini, A, Russello, M, Russo, G, Sacco, R, Sangiovanni, V, Schiano, A, Sciambra, A, Scifo, G, Simeone, F, Sullo, A, Tarquini, P, Tundo, P, and Vallone, A.
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viruses ,Hepatitis C virus ,Observational Study ,Antiviral therapy ,Boceprevir ,Chronic hepatitis ,Peg-interferon ,Ribavirin ,Telaprevir ,Hepatology ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,030212 general & internal medicine ,Telaprevi ,business.industry ,Virology ,Peg interferon ,Chronic infection ,chemistry ,Chronic hepatiti ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
AIM:To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.
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- 2016
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123. 436 B lymphocyte activation in chronic HCV infection: Implications for autoimmune and lymphoproliferative disorders
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Cerino, A., Timo, L., Comolli, G., Cividini, A., Gulminetti, R., Bamaba, V., and Mondelli, M.U.
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- 2006
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124. Serum and CSF biomarkers in asymptomatic patients during primary HIV infection: a randomized study.
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Calcagno A, Cusato J, Cinque P, Marchetti G, Bernasconi D, Trunfio M, Bruzzesi E, Rusconi S, Gabrieli A, Muscatello A, Antinori A, Ripamonti D, Gulminetti R, Antonucci M, and Nozza S
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- Humans, Middle Aged, Male, Adult, Female, Aged, Glial Fibrillary Acidic Protein blood, Glial Fibrillary Acidic Protein cerebrospinal fluid, tau Proteins cerebrospinal fluid, tau Proteins blood, Young Adult, Brain-Derived Neurotrophic Factor blood, Brain-Derived Neurotrophic Factor cerebrospinal fluid, Adolescent, Oxazines therapeutic use, Heterocyclic Compounds, 3-Ring therapeutic use, Pyridones therapeutic use, Emtricitabine therapeutic use, Tenofovir therapeutic use, Darunavir therapeutic use, Piperazines, HIV Infections drug therapy, HIV Infections cerebrospinal fluid, HIV Infections blood, Biomarkers blood, Biomarkers cerebrospinal fluid, Neurofilament Proteins blood, Neurofilament Proteins cerebrospinal fluid
- Abstract
It is debated whether CNS involvement begins during acute human immunodeficiency virus (HIV) infection in persons without meningitis/encephalitis and whether specific antiretroviral drugs or combinations would be beneficial. Neurologically asymptomatic participants enrolled in a randomized and controlled study comparing three combination antiretroviral regimens (tenofovir alafenamide/emtricitabine plus dolutegravir; darunavir; or both) during primary HIV infection were enrolled. Serum and CSF were collected at baseline and at 12 and 48 (serum only) weeks after treatment initiation. Single molecule array was used to measure neurofilament light chain (NFL), total tau protein (Tau), brain-derived neurotrophic factor, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase. We assessed the longitudinal change in biomarkers over time, in addition to the change in the prevalence of serum NFL concentrations above previously published age-adjusted cut-offs (7 pg/ml if 5-18 years, 10 pg/ml if 18-51 years, 15 pg/ml if 51-61 years, 20 pg/ml if 61-70 years and 35 pg/ml if >70 years). Serum was available from 47 participants at all time points, and CSF was available from 13 participants at baseline and 7 at Week 12. We observed a significant direct serum-to-CSF correlation for NFL (ρ = 0.692, P = 0.009), GFAP (ρ = 0.659, P = 0.014) and brain-derived neurotrophic factor (ρ = 0.587, P = 0.045). Serum (ρ = 0.560, P = 0.046) and CSF NFL (ρ = 0.582, P = 0.037) concentrations were directly associated with CSF HIV RNA levels. We observed a significant decrease over time in serum NFL (P = 0.006) and GFAP (P = 0.006) but not in the other biomarkers. No significant difference was observed among the treatment arms. At baseline, serum and CSF age-adjusted NFL levels were above age-adjusted cut-offs in 23 (48.9%) and four participants (30.8%), respectively; considering serum NFL, this proportion was lower at Weeks 12 (31.9%, P = 0.057) and 48 (27.7%, P = 0.13). A relevant proportion of neurologically asymptomatic participants had abnormal CSF and serum NFL levels during primary HIV infection. NFL and GFAP decreased in serum following combination antiretroviral therapy without significant differences among the treatment arms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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125. Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study.
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Corti N, Menzaghi B, Orofino G, Guastavigna M, Lagi F, Di Biagio A, Taramasso L, De Socio GV, Molteni C, Madeddu G, Salomoni E, Pellicanò GF, Pontali E, Bellagamba R, Celesia BM, Cascio A, Sarchi E, Gulminetti R, Calza L, Maggi P, Cenderello G, Bandera A, Carleo MA, Falasca K, Ferrara S, Martini S, Guadagnino G, Angioni G, Bargiacchi O, Ricci ED, Squillace N, and Bonfanti P
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- Humans, Male, Female, Middle Aged, Adult, Risk Factors, Incidence, Reverse Transcriptase Inhibitors therapeutic use, Reverse Transcriptase Inhibitors adverse effects, Anti-HIV Agents therapeutic use, Anti-HIV Agents adverse effects, Cardiovascular Diseases, HIV Infections drug therapy, HIV Infections complications, HIV Integrase Inhibitors therapeutic use, HIV Integrase Inhibitors adverse effects
- Abstract
Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.
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- 2024
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126. Lower aids-related hospitalizations in women living with HIV multidrug resistance.
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Papaioannu Borjesson R, Galli L, Lolatto R, Menzaghi B, Feasi M, Gulminetti R, Fornabaio C, Cattelan AM, Bonora S, Lagi F, Zazzi M, Castagna A, and Spagnuolo V
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- Female, Humans, HIV Infections complications, HIV Infections drug therapy, Drug Resistance, Multiple, Viral, Hospitalization statistics & numerical data
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- 2024
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127. Impact of Treatment Adherence on Efficacy of Dolutegravir + Lamivudine and Dolutegravir + Tenofovir Disoproxil Fumarate/Emtricitabine: Pooled Week 144 Analysis of the GEMINI-1 and GEMINI-2 Clinical Studies.
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Fernvik E, Sierra Madero J, Espinosa N, Gulminetti R, Hagins D, Tsai HC, Man C, Sievers J, Grove R, Zolopa A, Wynne B, van Wyk J, and Ait-Khaled M
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- Humans, Lamivudine therapeutic use, Tenofovir therapeutic use, Emtricitabine therapeutic use, Oxazines therapeutic use, Heterocyclic Compounds, 3-Ring therapeutic use, Pyridones therapeutic use, Treatment Adherence and Compliance, HIV Infections drug therapy, Anti-HIV Agents therapeutic use
- Abstract
Competing Interests: E.F., C.M., J.S., A.Z., B.W., J.v.W., and M.A.-K. are employees of ViiV Healthcare and own stock in GSK. N.E. has received grants from Merck; honoraria for participation in presentations or educational events from Merck, Gilead, Janssen, and GSK; and travel support from Gilead, Janssen, and GSK; and has participated in data safety monitoring or advisory boards for Merck, Gilead, and GSK. RGulminetti has received grants from Gilead and ViiV Healthcare, which were paid to his institution; received consulting fees from AbbVie, Gilead, ViiV Healthcare, and Merck Sharp & Dohme; received honoraria from Gilead, ViiV Healthcare, and Merck Sharp & Dohme; provided expert testimony for Gilead and ViiV Healthcare; and received travel support from Gilead. D.H. has served as a principal investigator through her institution, received honoraria for participation in speakers bureaus, and received travel support from GSK/ViiV Healthcare; has participated in advisory boards for ViiV Healthcare; and serves on the Georgia ADAP committee. RGrove is an employee of and owns stock in GSK. J.S.M. and H.-C.T. have no conflicts of interest to disclose.
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- 2023
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128. Pillars of long-term antiretroviral therapy success.
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Taramasso L, Andreoni M, Antinori A, Bandera A, Bonfanti P, Bonora S, Borderi M, Castagna A, Cattelan AM, Celesia BM, Cicalini S, Cingolani A, Cossarizza A, D'Arminio Monforte A, D'Ettorre G, Di Biagio A, Di Giambenedetto S, Di Perri G, Esposito V, Focà E, Gervasoni C, Gori A, Gianotti N, Guaraldi G, Gulminetti R, Lo Caputo S, Madeddu G, Maggi P, Marandola G, Marchetti GC, Mastroianni CM, Mussini C, Perno CF, Rizzardini G, Rusconi S, Santoro M, Sarmati L, Zazzi M, and Maggiolo F
- Abstract
Background: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies., Methods: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care., Results: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed., Conclusions: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history., Competing Interests: Declaration of Competing Interest This study was supported by an unrestricted grant from Gilead. The company had no role in designing the study, collecting or analyzing the data, interpreting the results, or writing or approving the article. Outside the submitted work, LT attended advisory boards or served as consultant or received grants for conferences participations from Gilead Sciences, ViiV Healthcare and Janssen and research grants for her institution from Gilead Sciences; ADB has received speakers’ honoraria from Gilead, ViiV, Janssen-Cilag, has been advisor for ViiV, Janssen-Cilag, MSD and had received grant for research from Gilead. MS has received funds for attending symposia, speaking and organizing educational activities from ViiV Healthcare, Janssen-Cilag and Theratechnologies. EF received speakers’ honoraria, research grants and advisory board fees from Viiv Healthcare, Gilead Sciences, Merck Sharp & Dohme and SOBI. AC has received funding for scientific advisory boards, travel, or speaker honoraria from Gilead Sciences, ViiV healthcare, Janssen-cilag, MSD.GG received research grant and speaker honorarium from Gilead, ViiV, MERCK and Jansen and attended advisory boards of Gilead, ViiV and MERCK. MA received payment or honoraria for lectures, presentations, or educational events from Gilead Sciences, AbbVie, ViiV healthcare, Janssen and Tibotec, support for attending meetings and/or travel from Gilead Sciences, AbbVie, ViiV healthcare; he attended advisory boards of Gilead Sciences, Moderna, Astra Zeneca and Pfizer. SDG has received advisory board fees from Viiv Healthcare, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme. ADM has received grants for her instituition by Viiv gilead msd janssen and has received fees for advisory boards by Viiv, Gilead Sciences, MSD, Gsk, Pfizer. PM received grant for publication, advisory board fees, and conference hospitality from Gilead Science, advisory board fees from ViiV Healthcare, advisory board fees and conference hospitality from MSD and Janssen. SC has served as a paid consultant to Gilead Sciences, Janssen-Cilag, Merck and ViiV Healthcare and received research funding through National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS from Gilead Sciences. BMC reports honoraria for presentations and scientific advice from Gilead Sciences, Bristol Myers Squibb, AbbVie, ViiV Healthcare, Janssen‐Cilag, Mylan and MSD and research grants for his institution from Gilead Sciences, ViiV Healthcare and MSD. NG has received travel support, grants and honoraria from Gilead, MSD, ViiV Healthcare, Janssen-Cilag. LS received travel grants from Gilead, Merck, Pfizer, fee for lectures and expertise from Merck, Gilead, Abbvie, Angelini, research funding from Gilead. SR received travel grants from Gilead, Janssen, attended advisory boards from Merck, Gilead, ViiV, GSK and received research funding from Gilead, Janssen, ViiV. SLC has been advisor for Gilead, ViiV, Janssen-Cilag, GSK, MSD and Astra Zeneca, had received speakers’ honoraria from Gilead, ViiV, MSD, Astra Zeneca, GSK and Janssen-Cilag, had received support for travel meetings from Gilead, Janssen-Cilag, and ViiV, had received grant for research from Gilead. AG received speaker’s honoraria and fees for attending advisory boards from ViiV Healthcare, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, Bristol-Myers Squibb, GSK, Pfizer, Novartis and received research grants from ViiV, Bristol-Myers Squibb, GSK, MSD, Angelini, Janssen-Cilag and Gilead. AA has served as a paid consultant to Astra Zeneca, Gilead Sciences, GSK, Janssen-Cilag, Merck, Moderna, Pfizer, Roche, and ViiV Healthcare and received research funding through National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS from Astra Zeneca, Gilead Sciences and ViiV Healthcare. RG received grants from ViiV, Merck, Gilead, Abbvie, Janseen and research funding from ViiV. CM received grant from Gilead and attended advisory boards of Gilead Sciences, ViiV Healthcare, MSD, Janssen. MZ received grants for research and educational activities from Gilead Sciences, Merck Sharp and Dohme, Theratechnologies, ViiV Healthcare and received personal fees for advisory boards and speaker's bureau from Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Merck Sharp and Dohme, Theratechnologies and ViiV Healthcare. GiuM has been advisor for Gilead, ViiV, Shionogi, Angelini, had received speakers’ honoraria from Gilead, ViiV and had received support for travel meetings from Gilead, Janssen-Cilag, and ViiV. GD has been advisor for Gilead, ViiV, Janssen-Cilag, GSK, MSD and Pfizer, had received speakers’ honoraria from Gilead, ViiV, MSD, Pfizer and Janssen-Cilag, had received support for travel meetings from Gilead, and ViiV and had received grant for research from Gilead. PB received grants for advisory boards or or honoraria for lectures from Gilead, Viiv, Merck; Jannsen, Pfizer. CM attended adivisory board and/or received speaking honoraria from ViiV, MSD, Pfizer, Astra-Zeneca, Gilead, Janssen-Cilag, GSK. GioM Has been advisor for Gilead, ViiV, Janssen-Cilag, GSK, MSD and Astra Zeneca, had received speakers’ honoraria from Gilead, ViiV, MSD, Astra Zeneca, GSK and Janssen-Cilag and had received support for travel meetings from Gilead, Janssen-Cilag, and ViiV. GDP has received fees for lectures and participation to advisory boards from Abbvie, GS, ViiV, GSK, Pfizer, AZ, Roche, MSD, Janssen.SB has received speaker's fees, advisors boards' fees or research Grant from Viiv, Gilead Sciences, Merck-Sharp and Dome, Jannssen Cilag and Abbvie. GR has participated to advisory boards and/or received fees for lectures from Gilead Sciences. AbbVie, Angelini, Janssen, GSK, and ViiV Healthcare; he received grants/ research support from Abbvie, Gilead Sciences, MSD and GSK. VE has been advisor for Gilead, ViiV, Janssen-Cilag, MSD and Astra Zeneca, received speakers’ honoraria from Gilead, Astra Zeneca, GSK and Janssen-Cilag and received support for travel meetings from Gilead, Janssen-Cilag, and ViiV, received grant for research from Gilead MSD and ViiV. The other authors did not declare conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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129. Incident diabetes in course of antiretroviral therapy.
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Taramasso L, Squillace N, Ricci E, Menzaghi B, Orofino G, Socio GV, Molteni C, Martinelli CV, Madeddu G, Vichi F, Valsecchi L, Celesia BM, Maggi P, Rusconi S, Pellicanò GF, Cascio A, Sarchi E, Gulminetti R, Falasca K, Di Biagio A, and Bonfanti P
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- Humans, Male, Middle Aged, Female, Prospective Studies, Weight Gain, Anti-Retroviral Agents adverse effects, HIV Infections complications, HIV Infections drug therapy, HIV Infections epidemiology, Diabetes Mellitus chemically induced, Diabetes Mellitus epidemiology, Anti-HIV Agents adverse effects
- Abstract
Objective: Recent reports of excessive weight gain in people with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitors (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset., Design: Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort., Methods: All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM., Results: 4366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4 + 460 [interquartile range (IQR) 256-710] cells/mm 3 cells/mm 3 . During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05-1.50).Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 kg 1.03; 95% CI 1.01-1.04), as well as older age (aHR 1.03 by 1 year; 95% CI 1.01-1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95% CI 1.48-3.49), having untreated high blood pressure (aHR 2.90; 95% CI 1.30-6.45) and baseline blood glucose >100 mg/dl (aHR 5.47; 95% CI 3.82-7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM., Conclusions: Baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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130. Trajectories of CD4 + /CD8 + T-Cells Ratio 96 Weeks after Switching to Dolutegravir-Based Two-Drug Regimens: Results from a Multicenter Prospective Cohort Study.
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Taramasso L, Falletta A, Ricci E, Orofino G, Squillace N, Menzaghi B, De Socio GV, Molteni C, Pellicanò GF, Gulminetti R, Madeddu G, Sarchi E, Vichi F, Celesia BM, Bonfanti P, and Di Biagio A
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- Humans, Lamivudine therapeutic use, CD8-Positive T-Lymphocytes, Prospective Studies, Heterocyclic Compounds, 3-Ring therapeutic use, Emtricitabine therapeutic use, CD4-Positive T-Lymphocytes, HIV Infections drug therapy, Anti-HIV Agents therapeutic use
- Abstract
The aim of the present study was to evaluate CD4/CD8 dynamics in patients on dolutegravir (DTG)-based two-drug regimens (2DRs) and compare them with DTG-containing triple-drug regimens (3DRs). A prospective observational study was performed in the context of the SCOLTA cohort. Experienced PWH with HIV-RNA < 50 copies/mL were included if they were on the DTG-2DR, the DTG + tenofovir/emtricitabine (TDF/FTC) regimen, the DTG + tenofovir alafenamide (TAF)/FTC regimen, or the DTG + abacavir/lamivudine (ABC/3TC) regimen; they were followed-up for at least one year. A total of 533 PWH were enrolled, 120 in the DTG + 3TC group, 38 in the DTG + protease inhibitors (PI) group, 67 in the DTG + rilpivirine (RPV) group, 49 in the DTG + TDF/FTC group, 27 in the DTG + TAF/FTC group, and 232 in the DTG + ABC/3TC group. After one year, the CD4/CD8 ratio significantly increased in the PWH treated with DTG + 3TC (+0.08 ± 0.26), DTG + TDF/FTC (+0.1 ± 0.19), and DTG + ABC/3TC (+0.08 ± 0.25). At two years, the CD4/CD8 increase was confirmed for PWH on DTG + TDF/FTC (+0.16 ± 0.28) and DTG + ABC/3TC (+0.1 ± 0.3). In the SCOLTA cohort, PWH on 2DRs experienced a CD4/CD8 increase only in the DTG + 3TC group. Controlled studies with longer follow-up will clarify the long-term immunological and clinical impacts of DTG-2DR.
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- 2022
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131. Long-term outcome of lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients.
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Maggiolo F, Gulminetti R, Pagnucco L, Digaetano M, Cervo A, Valenti D, Callegaro A, and Mussini C
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- Antigens, Surface therapeutic use, Creatinine, Heterocyclic Compounds, 3-Ring adverse effects, Humans, Lamivudine adverse effects, Oxazines, Piperazines, Prospective Studies, Pyridones, RNA, Viral Load, Anti-HIV Agents adverse effects, HIV Infections, HIV-1
- Abstract
Background: The use of DTG-containing two-drug regimens is one of the most promising solutions to the need to ease the management of HIV treatment without harming its efficacy and safety. We report long- term results in patients switched, while virologically suppressed, to the combination of dolutegravir (DTG) plus lamivudine (3TC)., Methods: This is a prospective, clinical, uncontrolled cohort enrolling ART-experienced people living with HIV (PLWH) with HIV-RNA < 50 copies/ml for 6 months or longer, negative hepatitis B virus surface antigen, and without known M184V/I mutations. Kaplan-Meiers curves are used to describe persistency of virological suppression on therapy and a Cox regression model to evaluate baseline characteristics and the risk of stopping therapy., Results: 218 individuals switched their regimen since 2015. The mean estimated follow-up was of 64.3 months (95% CI 61.3-67.3) for approximately 1000 patient/years. After 5 years of follow-up, 77.1% were still on the DTG-3TC combination. No virologic failure was detected throughout the whole study period, and only 15 subjects presented single isolated viral blips above 50 copies/ml. Most patients stopped therapy because of reasons unrelated to study drugs (lost to follow-up; patients' decision; moved to other Centers), but due to the unselected nature of the casuistry; 11 subjects died in the 5 years of follow-up mostly because of pre-existing co-morbidities (6 neoplastic diseases and 2 end-stage liver disease). The median baseline CD4 count was 669 cells/mcl (IQR 483-927). After 5 years it raised to 899 cells/mcl (IQR 646-1160) (P < 0.001) without a significant change of CD8 counts that lowered from 767 cells/mcl (IQR 532-1034) to 683 cells/mcl (IQR 538-988). Consequently, the CD4/CD8 ratio varied from 0.93 (IQR 0.60-1.30) to 1.15 (IQR 0.77-1.45) (P < 0.0001). A non-significant (P = 0.320) increment of mean creatinine, 0.06 mg/dl in magnitude, was observed over the whole follow-up., Conclusion: These long-term results over 5 years reinforce the durability and good tolerability of DTG-3TC. Our results continue to support the recommended switch use of this 2DR as a well-accepted treatment option for ART-experienced PLWH., (© 2022. The Author(s).)
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- 2022
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132. Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?
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Maggi P, De Socio GV, Menzaghi B, Molteni C, Squillace N, Taramasso L, Guastavigna M, Gamboni G, Madeddu G, Vichi F, Cascio A, Sarchi E, Pellicanò G, Martinelli CV, Celesia BM, Valsecchi L, Gulminetti R, Cenderello G, Parisini A, Calza L, Falasca K, Orofino G, Ricci E, Di Biagio A, and Bonfanti P
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- Aged, Anti-Retroviral Agents adverse effects, Comorbidity, Cross-Sectional Studies, Female, Humans, Male, Bone Diseases, Metabolic complications, HIV Infections complications, HIV Infections drug therapy, HIV Infections epidemiology, Hypertension complications, Noncommunicable Diseases epidemiology, Osteoporosis complications, Osteoporosis epidemiology
- Abstract
Background: In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART)., Methods: To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years)., Results: In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex., Conclusions: Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age., (© 2022. The Author(s).)
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- 2022
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133. Impact of treatment adherence on efficacy of dolutegravir plus lamivudine and dolutegravir plus tenofovir disoproxil fumarate/emtricitabine: pooled analysis of the GEMINI-1 and GEMINI-2 clinical studies.
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Ait-Khaled M, Sierra Madero J, Estrada V, Gulminetti R, Hagins D, Tsai HC, Man C, Sievers J, Grove R, Zolopa A, Wynne B, and van Wyk J
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- Adult, Drug Therapy, Combination, Emtricitabine, Heterocyclic Compounds, 3-Ring, Humans, Lamivudine therapeutic use, Oxazines, Piperazines, Pyridones, RNA therapeutic use, Tenofovir, Treatment Adherence and Compliance, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1
- Abstract
Background: GEMINI-1 and GEMINI-2 (ClinicalTrials.gov, NCT02831673 and NCT02831764, respectively) are double-blind, multicenter, phase III studies that demonstrated the non-inferiority of once-daily dolutegravir + lamivudine to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL at 48, 96, and 144 weeks in treatment-naive adults with HIV-1 infection. Objective: We present a post hoc analysis of the impact of treatment adherence on Week 48 virologic response. Methods: Adherence was estimated using pill counts and categorized as ≥90% vs <90%. Unadjusted treatment differences with exact 95% CIs were derived for the proportion of participants with HIV-1 RNA <50 copies/mL within each adherence category, using Snapshot algorithm and last available on-treatment viral load through Week 48. Results: In each treatment group, 5% of participants had <90% adherence (dolutegravir + lamivudine group, 35/716; dolutegravir + tenofovir disoproxil fumarate/emtricitabine group, 34/717). The proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot) at Week 48 in the <90% adherence group was 69% in the dolutegravir + lamivudine group and 65% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group (analysis by last on-treatment viral load: 91% and 85%, respectively). Corresponding proportions in the ≥90% adherence group were 93% and 96% (analysis by last on-treatment viral load: 97% and 99%, respectively). Conclusions: Decreased adherence resulted in lower Week 48 virologic efficacy outcomes that were comparable between treatment groups. These results indicate that the robust antiviral activity and regimen forgiveness of dolutegravir + lamivudine is similar to dolutegravir-containing 3-drug regimens (see graphical abstract).
- Published
- 2021
134. Durability of Dolutegravir-Based Regimens: A 5-Year Prospective Observational Study.
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Taramasso L, De Vito A, Ricci ED, Orofino G, Squillace N, Menzaghi B, Molteni C, Gulminetti R, De Socio GV, Pellicanò GF, Sarchi E, Celesia BM, Calza L, Rusconi S, Valsecchi L, Martinelli CV, Cascio A, Maggi P, Vichi F, Angioni G, Guadagnino G, Cenderello G, Dentone C, Bandera A, Falasca K, Bonfanti P, Di Biagio A, and Madeddu G
- Subjects
- Cohort Studies, Female, Heterocyclic Compounds, 3-Ring, Humans, Middle Aged, Oxazines therapeutic use, Piperazines, Prospective Studies, Pyridones, Anti-HIV Agents adverse effects, HIV Infections drug therapy
- Abstract
This study evaluates the frequency and causes of dolutegravir (DTG) discontinuation along 5 years of follow-up, in both antiretroviral treatment (ART)-naive and experienced people living with HIV (PLWH). This is a prospective multi-center cohort study enrolling PLWH on DTG from July 2014 until November 2020. DTG-durability was investigated using the Kaplan-Meier survival curve. The Cox proportional-hazards model was used for estimating the hazard ratio (HR) of DTG discontinuation for any cause, and for adverse events (AEs). Nine hundred sixty-three PLWH were included, 25.3% were women and 28.0% were ART-naive. Discontinuations for any causes were 10.1 [95% confidence interval (95% CI) 8.9-11.5] per 100 person-years, similar in most regimens, with the apparent exception of tenofovir alafenamide/emtricitabine+DTG ( p < 0.0001). In the multivariable Cox regression model, non-Caucasian ethnicity, age ≥50 years, and lower estimated glomerular filtration rate (eGFR) were associated with a higher probability of DTG interruption. The incidence rate of virological failure was 0.4 (95% CI 0.2-0.7) per 100 person-years, while the estimated discontinuation rate for AEs was 4.0 (3.2-4.9) per 100 person-years. Thirty-four DTG interruptions were due to grade ≥3 events (10 central nervous system, 6 hypersensitivity, 3 renal, 3 myalgia/asthenia, 3 abdominal pain, 2 gastrointestinal, and 7 other events). People with lower body mass index, age ≥50 years, and lower eGFR were at higher risk of AEs, while dual combinations were protective (HR 0.41 compared with abacavir/lamivudine/DTG, 95% CI 0.22-0.77). In this prospective observational study, we found high DTG durability and a low rate of virological failures. Dual therapies seemed protective toward AEs and might be considered, when feasible, a suitable option to minimize drug interactions and improve tolerability.
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- 2021
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135. A challenging case of SARS-CoV-2- AIDS and Nocardiosis coinfection from the SMatteo COvid19 REgistry (SMACORE).
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Colaneri M, Lupi M, Sachs M, Ludovisi S, Di Matteo A, Pagnucco L, Gulminetti R, Mariani B, Fabbiani M, and Bruno R
- Subjects
- Humans, Pandemics, Registries, SARS-CoV-2, Acquired Immunodeficiency Syndrome, COVID-19, Coinfection, Nocardia Infections diagnosis
- Abstract
The COVID-19 pandemic is posing an unprecedented threat worldwide. One issue that has faltered, though, concerns the underestimated risk to trade all for COVID-19, misdiagnosing other potentially life-threatening diseases. Further still, the presence of respiratory symptoms in AIDS patients should stimulate more vigilant efforts to uncover other or additional infections. This case report highlights the pitfalls of diagnosing a rare pulmonary infection during the COVID-19 pandemic.
- Published
- 2021
136. Patients with chronic hepatitis C receiving treatment with direct acting antivirals: How is this population changing?
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Lombardi A, Colaneri M, Vijayagopal KA, Sambo M, Legnazzi P, Sacchi P, Zuccaro V, Maiocchi L, Maserati R, Gulminetti R, Pagnucco L, Novati S, Zanaboni D, Michelone G, Ludovisi S, Mondelli MU, and Bruno R
- Subjects
- Comorbidity, Female, Hepacivirus drug effects, Hepatitis C, Chronic complications, Humans, Italy epidemiology, Liver Cirrhosis virology, Male, Middle Aged, Retrospective Studies, Severity of Illness Index, Antiviral Agents therapeutic use, Emigrants and Immigrants statistics & numerical data, Hepatitis C, Chronic drug therapy, Liver Cirrhosis epidemiology, Sustained Virologic Response
- Abstract
Background and Aims: Direct acting antiviral agents (DAAs) have revolutionized the landscape of chronic hepatitis C (CHC) enabling treatment of all those infected. It remains to be determined how the characteristics of those receiving treatment are changing., Materials and Methods: We retrospectively analysed all the patients with CHC who received treatment with DAAs in a large referral centre since 01/01/2015. We stratified their demographic, clinical and virological characteristics at baseline and the sustained virological response (SVR) rates according to the year of treatment., Results: In the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p<0.001) whereas mean age increased from 59.8 to 62.2 years old (p=0.04). An increasing trend was observed in the foreign-born patients from 4.3% to 7.9%, without reaching statistical significance. The prevalence of comorbidities had also increased during the study period (p<0.001). Instead, the yearly number of experienced patients decreased significantly (p<0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p<0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P<0.05)., Conclusions: The population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates., Competing Interests: Conflict of interest None declared, (Copyright © 2020. Published by Elsevier Ltd.)
- Published
- 2021
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137. Adaptive Natural Killer Cell Functional Recovery in Hepatitis C Virus Cured Patients.
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Mele D, Oliviero B, Mantovani S, Ludovisi S, Lombardi A, Genco F, Gulminetti R, Novati S, Mondelli MU, and Varchetta S
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- Adult, Aged, Aged, 80 and over, Antibody-Dependent Cell Cytotoxicity genetics, Antiviral Agents therapeutic use, CD57 Antigens genetics, Female, Hepatitis C drug therapy, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic virology, Humans, K562 Cells, Liver virology, Liver Cirrhosis virology, Lymphocyte Activation, Male, Middle Aged, Antibody-Dependent Cell Cytotoxicity immunology, Hepacivirus immunology, Hepatitis C, Chronic immunology, Killer Cells, Natural immunology, Liver pathology
- Abstract
Background and Aims: Current evidence suggests that dysfunctional natural killer (NK) cell responses during hepatitis C virus (HCV) infection can be restored after viral eradication with direct acting antivirals (DAAs). However, the fate of the recently described adaptive NK cell population, endowed with increased ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), during HCV infection is poorly defined, while no study has explored the effects of DAAs on this NK subset., Approach and Results: We performed multicolor flow cytometry to investigate CD57
+ FcεRIγneg adaptive and FcεRIγpos conventional NK cell phenotype and function before and after DAA treatment in 59 patients chronically infected with HCV, 39 with advanced liver fibrosis, and 20 with mild-moderate liver fibrosis. Moreover, bulk NK cell phenotype and function were analyzed after cytokine activation following contact with K562 target cells. The proportion of FcεRIγneg NK cells in patients with HCV was associated with increased HCV load at baseline, and it was significantly reduced after treatment. Patients with an advanced fibrosis stage displayed increased NK cell activation and exhaustion markers that normalized after therapy. Of note, adaptive NK cells from patients with HCV were characterized by increased programmed death receptor 1 expression and reduced ADCC activity at baseline. DAA treatment restored ADCC ability and reduced programmed death receptor 1 expression., Conclusions: HCV profoundly affects the frequency, phenotype, and function of adaptive NK cells. DAA therapy restores a normal adaptive NK phenotype and enhances interferon-gamma production by this cell subset., (© 2020 by the American Association for the Study of Liver Diseases.)- Published
- 2021
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138. Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.
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Taramasso L, Fabbiani M, Nozza S, De Benedetto I, Bruzzesi E, Mastrangelo A, Pinnetti C, Calcagno A, Ferrara M, Bozzi G, Focà E, Quiros-Roldan E, Ripamonti D, Campus M, Celesia BM, Torti C, Cosco L, Di Biagio A, Rusconi S, Marchetti G, Mussini C, Gulminetti R, Cingolani A, d'Ettorre G, Madeddu G, Franco A, Orofino G, Squillace N, Muscatello A, Gori A, Antinori A, Tambussi G, and Bandera A
- Subjects
- Acute Disease, Adult, Anti-HIV Agents pharmacology, CD4 Lymphocyte Count, Female, HIV Infections blood, HIV Infections virology, HIV-1 drug effects, Humans, Italy, Male, Middle Aged, RNA, Viral genetics, Regression Analysis, Retrospective Studies, Risk Factors, Treatment Failure, Viral Load drug effects, Anti-HIV Agents therapeutic use, Central Nervous System Diseases etiology, HIV Infections drug therapy, HIV-1 genetics
- Abstract
Objectives: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI)., Methods: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR., Results: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR., Conclusions: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients., (© 2020 British HIV Association.)
- Published
- 2020
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139. Baseline Amino Acid Substitutions in the NS5A ISDR and PKR Binding Domain of Hepatitis C and Different Fibrosis Levels and Levels of Development of Hepatocellular Carcinoma in Patients Treated with DAAs.
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Paolucci S, Piralla A, Novazzi F, Fratini A, Maserati R, Gulminetti R, Novati S, Barbarini G, Sacchi P, Silvestri A, and Baldanti F
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- Aged, Carcinoma, Hepatocellular etiology, Computational Biology methods, Female, Hepatitis C, Chronic complications, Humans, Liver Cirrhosis diagnosis, Liver Cirrhosis etiology, Liver Neoplasms etiology, Male, Middle Aged, Protein Binding, RNA, Viral, Viral Nonstructural Proteins chemistry, Hepacivirus physiology, Hepatitis C, Chronic metabolism, Hepatitis C, Chronic virology, Host-Pathogen Interactions, Protein Interaction Domains and Motifs, Viral Nonstructural Proteins genetics, Viral Nonstructural Proteins metabolism
- Abstract
Variations in the interferon sensitivity-determining region (ISDR) within the NS5A region were related to the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). The aim of the study was to investigate a relationship between ISDR/PKR substitutions and their association with liver fibrosis or HCC development. A total of 316 patients infected with HCV and treated with DAAs were evaluated. HCV RNA was quantified and sequenced before treatment. The liver fibrosis stage was assessed by transient elastography and equalized to METAVIR scores. Multivariate analysis showed that ≥3 substitutions in ISDR and ≥6 in PKR-bd were significantly associated with advanced fibrosis. Advanced fibrosis was observed in patients with higher substitutions in ISDR and PKR-bd. A higher correlation between advanced fibrosis and a high frequency of ≥3 substitutions in ISDR and ≥6 in PKR-bd was observed in patients infected with genotype 2c. In addition, in a higher proportion of HCC patients, advanced fibrosis (40.4% vs. 88.2%; p < 0.001) and ≥6 substitutions in PKR-bd (15.4% vs. 41.2%; p = 0.01) was observed. In conclusion, a higher number of substitutions in ISDR and PKR-bd were associated with advanced liver fibrosis, suggesting a use of like predictors for progression in the liver damage. A significantly higher number of PKR-bd substitutions was observed in HCC patients; in particular, in patients infected with HCV genotype 2c.
- Published
- 2020
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140. Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection-Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study.
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Muscatello A, Nozza S, Fabbiani M, De Benedetto I, Ripa M, Dell'acqua R, Antinori A, Pinnetti C, Calcagno A, Ferrara M, Focà E, Quiros-Roldan E, Ripamonti D, Campus M, Maurizio Celesia B, Torti C, Cosco L, Di Biagio A, Rusconi S, Marchetti G, Mussini C, Gulminetti R, Cingolani A, D'ettorre G, Madeddu G, Franco A, Orofino G, Squillace N, Gori A, Tambussi G, and Bandera A
- Abstract
Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation., Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers., Methods: This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥500/µL, CD4 ≥30%, and CD4/CD8 ≥1), and first-line ART regimen discontinuation by Cox regression analysis., Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log
10 copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs., Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control., Competing Interests: Giulia Marchetti serves as an associate editor for Pathogens and Immunity., (© Pathogens and Immunity 2020.)- Published
- 2020
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141. Switch to dolutegravir and unboosted atazanavir in HIV-1 infected patients with undetectable viral load and long exposure to antiretroviral therapy.
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Castagna A, Rusconi S, Gulminetti R, Bonora S, Mazzola G, Quiros-Roldan ME, De Socio GV, Ladisa N, Carosella S, Cattelan A, Di Giambenedetto S, Mena M, Poli A, Galli L, and Riva A
- Subjects
- Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Therapy, Combination, Female, HIV-1 drug effects, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Oxazines, Piperazines, Pyridones, RNA, Viral blood, Treatment Outcome, Viral Load, Atazanavir Sulfate therapeutic use, Drug Substitution, HIV Infections drug therapy, HIV Integrase Inhibitors therapeutic use, Heterocyclic Compounds, 3-Ring therapeutic use
- Abstract
: We evaluated the efficacy and safety of a two-drug regimen including dolutegravir (DTG) and unboosted atazanavir (uATV) in 151 HIV-1 infected patients with HIV-RNA of more than 50 copies/ml. During a median follow-up of 62 (42-97) weeks, two virological failures (1%) and 13 treatment discontinuations (9%) occurred; the 48-week probability of virological failure was 0.8% (95% confidence interval 0.2-5.6%). Switch to DTG + uATV may represent a boosting and transcriptase reverse inhibitors sparing otion in individuals with long exposure to antiretroviral therapy and risk of cardiovascular disease.
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- 2019
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142. Correction: Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study.
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Kondili LA, Gaeta GB, Ieluzzi D, Zignego AL, Monti M, Gori A, Soria A, Raimondo G, Filomia R, Di Leo A, Iannone A, Massari M, Corsini R, Gulminetti R, Gatti Comini A, Toniutto P, Dissegna D, Russo FP, Zanetto A, Rumi MG, Brancaccio G, Danieli E, Brunetto MR, Weimer LE, Quaranta MG, Vella S, and Puoti M
- Abstract
[This corrects the article DOI: 10.1371/journal.pone.0172159.].
- Published
- 2018
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143. Baseline and Breakthrough Resistance Mutations in HCV Patients Failing DAAs.
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Paolucci S, Premoli M, Novati S, Gulminetti R, Maserati R, Barbarini G, Sacchi P, Piralla A, Sassera D, De Marco L, Girello A, Mondelli MU, and Baldanti F
- Subjects
- Drug Resistance, Viral genetics, Genotype, Hepacivirus drug effects, Hepacivirus pathogenicity, Hepatitis C, Chronic genetics, High-Throughput Nucleotide Sequencing, Humans, Mutation, Sustained Virologic Response, Treatment Failure, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy
- Abstract
Sustained virologic response rates have increased dramatically following direct acting antiviral (DAA) therapy in chronic HCV infection. However, resistance-associated substitutions (RASs) may occur either prior to DAA or following drug exposure. The aim of this study was to determine RASs in DAA treatment-failing patients and the role of RASs in failure treatment. Six hundred and twenty HCV patients were evaluated. Direct sequencing of HCV genes was performed at breakthrough in all 31 patients failing DAAs, and in 19 baseline patients. Deep sequencing analysis was performed in 15/19 baseline patients. RASs were detected at breakthrough in 17/31 patients and at baseline in 11/19 patients, although, only 8/19 patients carried RASs associated with the prescribed regimen. Deep sequencing analysis showed RASs at baseline in 10/15 treatment-failing patients. No significant difference was observed with the Sanger sequencing. Treatment failure in the 14/31 patients without RASs was associated with suboptimal treatment. In 54.8% of treatment-failing patients one of the causes of failure might be the presence of RASs. In the majority of patients with RASs, mutations were present at baseline. Direct resistance test is advocated before treatment and at breakthrough in order to optimize retreatment regimens.
- Published
- 2017
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144. Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients.
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Maggiolo F, Gulminetti R, Pagnucco L, Digaetano M, Benatti S, Valenti D, Callegaro A, Ripamonti D, and Mussini C
- Subjects
- CD4 Lymphocyte Count, Comorbidity, Drug Therapy, Combination, Female, HIV Infections immunology, HIV Infections physiopathology, Humans, Male, Middle Aged, Oxazines, Piperazines, Prospective Studies, Pyridones, RNA, Viral blood, Treatment Outcome, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Heterocyclic Compounds, 3-Ring therapeutic use, Lamivudine therapeutic use, Viral Load drug effects
- Abstract
Background: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients., Methods: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART., Results: Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10)., Discussion: Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms., Conclusion: Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials.
- Published
- 2017
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145. Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study.
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Kondili LA, Gaeta GB, Ieluzzi D, Zignego AL, Monti M, Gori A, Soria A, Raimondo G, Filomia R, Di Leo A, Iannone A, Massari M, Corsini R, Gulminetti R, Gatti Comini A, Toniutto P, Dissegna D, Russo FP, Zanetto A, Rumi MG, Brancaccio G, Danieli E, Brunetto MR, Weimer LE, Quaranta MG, Vella S, and Puoti M
- Subjects
- Adult, Aged, Aged, 80 and over, Drug Administration Schedule, Drug Therapy, Combination, Female, Hepacivirus, Humans, Interferons, Italy, Liver Cirrhosis chemically induced, Liver Cirrhosis complications, Male, Middle Aged, Prospective Studies, Risk, Antiviral Agents adverse effects, Antiviral Agents therapeutic use, Drug Interactions, Hepatitis C, Chronic drug therapy
- Abstract
Background: There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used., Aim: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study., Methods: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org)., Results: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI., Conclusions: Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.
- Published
- 2017
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146. Discontinuation of treatment and adverse events in an Italian cohort of patients on dolutegravir.
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Bonfanti P, Madeddu G, Gulminetti R, Squillace N, Orofino G, Vitiello P, Rusconi S, Celesia BM, Maggi P, and Ricci E
- Subjects
- Cohort Studies, HIV Integrase Inhibitors, Humans, Oxazines, Piperazines, Pyridones, HIV Infections, Heterocyclic Compounds, 3-Ring
- Published
- 2017
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147. Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience.
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Cleo Study Group, Ascione A, Adinolfi LE, Amoroso P, Andriulli A, Armignacco O, Ascione T, Babudieri S, Barbarini G, Brogna M, Cesario F, Citro V, Claar E, Cozzolongo R, D'Adamo G, D'Amico E, Dattolo P, De Luca M, De Maria V, De Siena M, De Vita G, Di Giacomo A, De Marco R, De Stefano G, De Stefano G, Di Salvo S, Di Sarno R, Farella N, Felicioni L, Fimiani B, Fontanella L, Foti G, Furlan C, Giancotti F, Giolitto G, Gravina T, Guerrera B, Gulminetti R, Iacobellis A, Imparato M, Iodice A, Iovinella V, Izzi A, Liberti A, Leo P, Lettieri G, Luppino I, Marrone A, Mazzoni E, Messina V, Monarca R, Narciso V, Nosotti L, Pellicelli AM, Perrella A, Piai G, Picardi A, Pierri P, Pietromatera G, Resta F, Rinaldi L, Romano M, Rossini A, Russello M, Russo G, Sacco R, Sangiovanni V, Schiano A, Sciambra A, Scifo G, Simeone F, Sullo A, Tarquini P, Tundo P, and Vallone A
- Abstract
Aim: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings., Methods: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL)., Results: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age., Conclusion: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.
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- 2016
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148. Development and persistence of DAA resistance associated mutations in patients failing HCV treatment.
- Author
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Paolucci S, Fiorina L, Mariani B, Landini V, Gulminetti R, Novati S, Maserati R, Barbarini G, Bruno R, and Baldanti F
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- Genotype, Hepacivirus classification, Hepacivirus drug effects, Hepacivirus isolation & purification, Humans, Oligopeptides administration & dosage, Oligopeptides pharmacology, Proline administration & dosage, Proline analogs & derivatives, Proline pharmacology, Sequence Analysis, DNA, Treatment Failure, Viral Nonstructural Proteins genetics, Antiviral Agents administration & dosage, Antiviral Agents pharmacology, Drug Resistance, Viral, Hepacivirus genetics, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic virology, Mutation, Missense
- Abstract
Background: Direct-acting antiviral agents (DAAs) combined with pegylated-interferon (PegIFN) and ribavirin (RBV) are still a standard treatment in patients with genotype 1HCV infection. However, virologic response could be impaired by baseline or early selection of resistant HCV strains., Objectives: The aim of this study was to determine the onset and persistence of resistance-associated mutations (RAMs) in the NS3 and NS5B genes of DAA-naïve patients failing treatment., Study Design: Direct sequencing of HCV NS3 was performed in 49 DAA-naïve patients with HCV genotype 1 infection., Results: Eight out of 23 patients (34.7%) failed PegIFN/RBV/telaprevir during the 12-weeks of therapy. Treatment failure was associated with the development of RAMs at amino-acids 36,54,80 and 155 of the HCV protease in 6/8 patients (75%). Among patients treated with PegIFN/RBV/boceprevir treatment, 4/18 (22.2%) failed therapy. Of these, 2 (50%) carried virus strains which developed a RAM at amino-acids 54 and 155. Among HCV strains with RAMs, 7 belonged to genotype 1a and 1 to 1b. Finally, in 6/10 (60%) patients, drug-resistant variants could still be detected for up to 3-7 months after stopping therapy., Conclusions: A higher rate (p=0.49) of treatment failure was observed in patients receiving telaprevir- compared to the boceprevir-based combination. In addition, compared with genotype 1b, genotype 1a was associated with higher rates (p=0.01) of treatment failure due to virus resistant strains. Resistance testing at baseline and during DAA treatment should be taken into consideration when treating patients with new HCV combination therapies., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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149. Phylogenetic analysis of HIV type 1 CRF02_AG in multiple genes in Italian and African patients living in Italy.
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Paolucci S, Piralla A, Fiorina L, Gulminetti R, Novati S, Lai A, and Baldanti F
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- Africa, Western, Cluster Analysis, Cuba, Emigrants and Immigrants, Evolution, Molecular, Genotype, HIV-1 isolation & purification, Humans, Italy, Molecular Sequence Data, Mutation Rate, Phylogeny, Sequence Analysis, DNA, Genes, Viral, Genetic Variation, HIV Infections virology, HIV-1 classification, HIV-1 genetics
- Abstract
Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 02_AG is a major recombinant variant in different geographic areas and is predominant in West and Central Africa. Of particular interest is the increased frequency of CRF02_AG in patients living in Italy. In the present study, phylogenetic analyses were performed on gag, pol (integrase), and env (gp120 and gp41) gene sequences from 34 CRF02_AG-infected patients living in Italy. Thirty out of 34 (89.4%) patients were from western Africa, 3/34 (8.8%) were born in Italy, and 1/34 (2.9%) was from Cuba. Phylogenetic analysis revealed the presence of a well-supported clade (aLRT score>0.75) of sequences only in gp120 and gp41 trees. Evolutionary rate estimation showed a faster evolution for the gp120 gene with respect to the gag, integrase, and gp41 genes. This finding was confirmed by the analysis of interpatient variability. Intrapatient variability was greater in gp120 gene sequences; 10/19 (52.6%; p<0.001) patients had a ratio of dN/dS>1 as compared with gag, integrase, and gp41 gene sequences with dN/dS ratios<1. In summary, phylogenetic analyses of CRF02_AG strains offer a perspective on intrapatient and interpatient variability among CRF02_AG-infected patients living in Italy. In addition, divergent phylogenetic relationships were observed among different genomic regions.
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- 2014
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150. Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B HBeAg negative genotype D patients and risk for hepatocellular carcinoma.
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Pellicelli AM, Vignally P, Messina V, Izzi A, Mazzoni E, Barlattani A, Bacca D, Romano M, Mecenate F, Stroffolini T, Furlan C, Picardi A, Gentilucci UV, Gulminetti R, Bonaventura ME, Villani R, D'Ambrosio C, Paffetti A, Mastropietro C, Marignani M, Fondacaro L, Cerasari G, Andreoli A, and Barbarini G
- Subjects
- Adenine analogs & derivatives, Adenine therapeutic use, Adult, Aged, Cohort Studies, DNA, Viral genetics, Female, Guanine analogs & derivatives, Guanine therapeutic use, Hepatitis B e Antigens immunology, Hepatitis B virus genetics, Hepatitis B, Chronic complications, Hepatitis B, Chronic immunology, Humans, Lamivudine therapeutic use, Longitudinal Studies, Male, Middle Aged, Organophosphonates therapeutic use, Retrospective Studies, Telbivudine, Tenofovir, Thymidine analogs & derivatives, Thymidine therapeutic use, Viral Load, Antiviral Agents therapeutic use, Carcinoma, Hepatocellular etiology, Hepatitis B, Chronic drug therapy, Liver Neoplasms etiology
- Abstract
Unlabelled: BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded., Results: HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003)., Conclusions: Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.
- Published
- 2014
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