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1. Impact of therapeutic drug monitoring of antiretroviral drugs in routine clinical management of patients infected with human immunodeficiency virus and related health care costs: a real-life study in a large cohort of patients

Author

Perrone V, Cattaneo D, Radice S, Sangiorgi D, Federici AB, Gismondo MR, Medaglia M, Micheli V, Vimercati S, Pallone E, Degli Esposti L, and Clementi E

Subjects
Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Valentina Perrone,1 Dario Cattaneo,1 Sonia Radice,1 Diego Sangiorgi,2 Augusto B Federici,3 Maria Rita Gismondo,4 Massimo Medaglia,5 Valeria Micheli,4 Stefania Vimercati,5 Enza Pallone,6 Luca Degli Esposti,2 Emilio Clementi1,71Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, L Sacco University Hospital, University of Milan, Milan, 2CliCon Srl, Health, Economics and Outcomes Research, Ravenna, 3Hematology and Transfusion Medicine, Department of Clinical Sciences and Community Health, 4Clinical Microbiology Virology and Diagnosis of Bioemergency, 5Pharmaceutical Department, 6Quality Clinical Risk and Accreditation Unit, L Sacco University Hospital, Milan, 7Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, ItalyBackground: Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV). Studies have documented high interindividual variability in the pharmacokinetics of antiretroviral drugs, which may impair the success of HAART if not managed properly. Therapeutic drug monitoring (TDM) is a useful diagnostic tool that helps clinicians to optimize drug doses so that drug concentrations associated with the highest therapeutic efficacy are obtained with a reduced risk of concentration-dependent adverse effects. The aim of this study was to assess whether use of TDM improves clinical outcomes and cost of illness.Methods: A retrospective cohort study was conducted at L Sacco University Hospital in Milan, Italy, in HIV-infected patients aged ≥18 years with at least one prescription of antiretroviral drugs for which TDM was applied. The inclusion period was from January 2010 to December 2011, with a follow-up period of up to 12 months. Laboratory and administrative databases were analyzed and matched with each other.Results: The cohort consisted of 5,347 patients (3,861 males and 1,486 females) of mean age 43.9±12.5 years. We found that TDM had been used in 143 of these patients, among whom adherence with therapy was significantly higher than among those in whom TDM had not been used (94% versus 78%). In TDM-controlled patients, the mean length of HIV-related hospitalization stay and mean cost of hospitalization were significantly reduced with respect to those observed in the group in which TDM had not been used (7.21 days versus 29.47 days and €293 versus €688, respectively).Conclusion: Inclusion of TDM as part of routine clinical optimization of drug dosing in HIV-infected patients is associated with higher adherence to therapy, reduced length of hospitalization stay, and reduced cost of illness.Keywords: human immunodeficiency virus, therapeutic drug monitoring, health care costs

Published
2014

3. Erratum: Imported arboviral infections in Italy, July 2014-October 2015: A National Reference Laboratory report [BMC Infect. Dis. 17, (2017)(216)] DOI: 10.1186/s12879-017-2320-1

Author

Fortuna, C, Remoli, Me, Rizzo, C, Benedetti, E, Fiorentini, C, Bella, A, Argentini, C, Farchi, F, Castilletti, C, Capobianchi, Mr, Zammarchi, L, Bartoloni, A, Zanchetta, N, Gismondo, Mr, Nelli, Lc, Vitale, G, Baldelli, F, D'Agaro, P, Sodano, G, Rezza, G, and Arbovirus Working Group, Venturi G

Subjects
Infectious Diseases
Published
2017

5. Declining Prevalence of HIV-1 Drug Resistance in Antiretroviral Treatment-exposed Individuals in Western Europe

Author

De Luca, A, Dunn, D, Zazzi, M, Camacho, R, Torti, C, Fanti, I, Kaiser, R, Sönnerborg, A, Codoñer, Fm, Van Laethem, K, Vandamme, Am, Bansi, L, Ghisetti, V, van de Vijver DA, Asboe, D, Prosperi, Mc, Di Giambenedetto, S, Collaborators: Giacometti A, SEHERE collaboration in C. h. a. i. n., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, Ad, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, De Luca, A, Dunn, D, Zazzi, M, Camacho, R, Torti, C, Fanti, I, Kaiser, R, Sönnerborg, A, Codoñer, F, Van Laethem, K, Vandamme, A, Bansi, L, Ghisetti, V, Van De Vijver, D, Asboe, D, Prosperi, M, Di Giambenedetto, S, Mancuso, S, and Virology

Subjects
Male, Multivariate analysis, Databases, Factual, Drug Resistance, HIV Infections, Drug resistance, 0302 clinical medicine, Retrospective Studie, Risk Factors, Epidemiology, Genotype, pol Gene Products, Human Immunodeficiency Viru, Odds Ratio, Prevalence, Immunology and Allergy, HIV Infection, 030212 general & internal medicine, pol Gene Products, Viral, Multivariate Analysi, media_common, 0303 health sciences, Drug Resistance Prevalence HIV-1, Middle Aged, Resistance mutation, 3. Good health, Reverse Transcriptase Inhibitor, Europe, Infectious Diseases, Reverse Transcriptase Inhibitors, epidemiology, Female, Multiple, Human Immunodeficiency Virus, Human, Drug, Adult, medicine.medical_specialty, Evolution, media_common.quotation_subject, Sexual Behavior, antiretroviral therapy, Infectious Disease, Biology, Settore MED/17 - MALATTIE INFETTIVE, Evolution, Molecular, 03 medical and health sciences, Databases, SDG 3 - Good Health and Well-being, Drug Resistance, Multiple, Viral, medicine, Humans, HIV Protease Inhibitor, Factual, Retrospective Studies, 030306 microbiology, Risk Factor, Molecular, Retrospective cohort study, Odds ratio, HIV Protease Inhibitors, CD4 Lymphocyte Count, drug resistance, genotyping, HIV-1, Multivariate Analysis, Mutation, pol Gene Products, Human Immunodeficiency Virus, Immunology, Demography
Abstract

HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis. © 2013 The Author.

Published
2013
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6. Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis

Author

Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, MANCUSO, Salvatrice, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, Poletti, F., Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, and Poletti, F

Subjects
Male, Time Factors, Cross-sectional study, Human immunodeficiency virus (HIV), Drug Resistance, HIV Infections, Drug resistance, medicine.disease_cause, Cohort Studies, Antiretroviral Therapy, Highly Active, Ritonavir-boosted darunavir, Genotype, HIV Infection, Treatment Failure, Viral, Genotypic resistance, Darunavir, Sulfonamides, General Medicine, Middle Aged, Virological failure, Infectious Diseases, Female, Human, medicine.drug, Adult, Microbiology (medical), Logistic Model, Time Factor, Antiretroviral Therapy, Settore MED/17 - MALATTIE INFETTIVE, Sulfonamide, Drug Resistance, Viral, medicine, Humans, Highly Active, Protease inhibitors, Cross-Sectional Studies, HIV Protease Inhibitors, HIV-1, Logistic Models, Mutation, HIV Protease Inhibitor, Cross-Sectional Studie, business.industry, Antiretroviral therapy, Virology, Protease inhibitor, Cohort Studie, business
Abstract

Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. Discussion The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. Conclusion: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon. © Springer-Verlag 2011.

Published
2012

7. A novel methodology for large-scale phylogeny partition

Author

Prosperi, Mattia C. F., Ciccozzi, Massimo, Fanti, Iuri, Saladini, Francesco, Pecorari, Monica, Borghi, Vanni, Di Giambenedetto, Simona, Bruzzone, Bianca, Capetti, Amedeo, Vivarelli, Angela, Rusconi, Stefano, Maria Carla, Re, Gismondo, Maria Rita, Sighinolfi, Laura, Gray, Rebecca R., Salemi, Marco, Zazzi, Maurizio, De Luca, Andrea, Giacometti, A, Butini, L, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, De Luca, A, Fadda, G, Vullo, Vincenzo, Turriziani, Ombretta, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Delle Foglie, P, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E., Prosperi MC, Ciccozzi M, Fanti I, Saladini F, Pecorari M, Borghi V, Di Giambenedetto S, Bruzzone B, Capetti A, Vivarelli A, Rusconi S, Re MC, Gismondo MR, Sighinolfi L, Gray RR, Salemi M, Zazzi M, De Luca A, ARCA collaborative group., Prosperi, M, Ciccozzi, M, Fanti, I, Saladini, F, Pecorari, M, Borghi, V, Di Giambenedetto, S, Bruzzone, B, Capetti, A, Vivarelli, A, Rusconi, S, Re, M, Gismondo, M, Sighinolfi, L, Gray, R, Salemi, M, Zazzi, M, De Luca, A, and Mancuso, S

Subjects
Genetics and Molecular Biology (all), Male, pol, Theoretical computer science, Inference, Gene Products, pol, General Physics and Astronomy, HIV Infections, Biology, Network topology, Settore MED/17 - MALATTIE INFETTIVE, Biochemistry, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Physics and Astronomy (all), 0302 clinical medicine, Search algorithm, phylogenetic analysis, virus transmission, Gene Products, Humans, HIV Infection, 030212 general & internal medicine, Phylogeny, 030304 developmental biology, Algorithms, Classification, Female, HIV-1, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Genetics, 0303 health sciences, Multidisciplinary, Phylogenetic tree, Node (networking), HIV, General Chemistry, Partition (database), Algorithm, Identification (information), Transmission (telecommunications), METHODOLOGY, Human
Abstract

Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny of 11,541 human immunodeficiency virus-1 subtype B pol gene sequences from a large Italian cohort. Molecular transmission chains were characterized by means of different clinical/demographic factors, such as the interaction between male homosexuals and male heterosexuals. Our method takes an advantage of a flexible notion of transmission cluster and can become a general framework to analyse other epidemics. © 2011 Macmillan Publishers Limited. All rights reserved.

Published
2011
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8. No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy

Author

Gianotti, N1, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Collaborators Giacometti A, ARCA database i. n. i. t. i. a. t. i. v. e., Butini, L, del Gobbo, R, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Gianotti, N, Cicconi, P, Rusconi, S, Gismondo, Mr, Biondi, Ml, Capetti, A, Boeri, E, Pecorari, M, Mussini, C, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Antinori, A, Vullo, Vincenzo, Turriziani, O, Perno, Cf, Montano, M, Cenderello, G, Gonnelli, A, Romano, L, Palumbo, M, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, Lattuada, E., Gianotti, N, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Mancuso, S, Gianotti N, Galli L, Zazzi M, Ghisetti V, Bonora S, Micheli V, Meraviglia P, Corsi P, Bruzzone B, Menzo S, Di Giambenedetto S, De Luca A, Filice G, Penco G, Castagna A, Giacometti A, Butini L, del Gobbo R, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Callegaro A, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Paolini E, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Di Pietro M, Bartalesi F, Colao G, Tosti A, Di Biagio A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Gianotti, Nicola, Galli, Laura, Zazzi, Maurizio, Ghisetti, Valeria, Bonora, Stefano, Micheli, Valeria, Meraviglia, Paola, Corsi, Paola, Bruzzone, Bianca, Menzo, Stefano, Di Giambenedetto, Simona, De Luca, Andrea, Filice, Gaetano, Penco, Giovanni, and Castagna, Antonella

Subjects
Male, HIV Infections, Drug resistance, Logistic regression, Resistance to nucleoside reverse transcriptase inhibitor, CD4+ T-lymphocyte, Retrospective Studie, Immunopathology, Antiretroviral Therapy, Highly Active, Resistance to non-nucleoside reverse transcriptase inhibitor, genetics, Resistance to protease inhibitor, HIV Infection, resistance to nucleoside reverse transcriptase inhibitors, Viral, Sida, resistance to protease inhibitors, biology, Reverse-transcriptase inhibitor, Viral Load, Genes, pol, drug therapy/immunology/virology, Reverse Transcriptase Inhibitor, Infectious Diseases, Treatment Outcome, resistance to non-nucleoside reverse transcriptase inhibitors, Reverse Transcriptase Inhibitors, Female, Viral load, medicine.drug, Human, pol, Anti-HIV Agents, Antiretroviral Therapy, Viremia, Infectious Disease, Settore MED/17 - MALATTIE INFETTIVE, pharmacology/therapeutic use, Acquired immunodeficiency syndrome (AIDS), Virology, Drug Resistance, Viral, medicine, Humans, Highly Active, Retrospective Studies, pharmacology/therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, genetics, Female, Genes, pol, HIV Infections, drug therapy/immunology/virology, HIV-1, drug effects/enzymology/genetics, Humans, Male, Mutation, Retrospective Studies, Reverse Transcriptase Inhibitors, therapeutic use, Treatment Outcome, Viral Load, drug resistance, Anti-HIV Agent, biology.organism_classification, medicine.disease, CD4 Lymphocyte Count, Genes, drug effects/enzymology/genetics, therapeutic use, Mutation, CD4+ T-lymphocytes, HIV-1
Abstract

An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression 50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analysis. Median (Q1, Q3) values at baseline were the following: age 40 (37, 45) years, years on antiretroviral therapy 4.45 (3.65, 5.47), HIV RNA 3.91 (3.39, 4.53) log 10 copies/ml, CD4+ T-cell 358 (211, 524)/μl. After 3.13 years of follow-up, 375 patients (45.4%) showed a lack of immune recovery. The risk of lack of immune recovery increased independently with increasing baseline CD4+ counts (OR=1.104 per 50-cell increase, 95% CI=1.069-1.142, P

Published
2011

9. Low Rate of Virological Failure and Maintenance of Susceptibility to HIV-1 Protease Inhibitors with First-Line Lopinavir/Ritonavir-Based Antiretroviral Treatment in Clinical Practice

Author

Prosperi, Mc, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, Mr, Bagnarelli, P, Carli, T, De Luca, A, ARCA Collaborative Group, Giacometti, A, Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Raffaele, P, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, A, Cicconi, P, Rusconi, S, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, Clinic of Infectious Diseases, Università cattolica del Sacro Cuore [Roma] (Unicatt), Molecular Biology, Microbiology and Virology, Bari University Hospital, Clinical Infectious Diseases, Careggi University Hospital, Unit of Infectious Diseases, Catholic Universisty of Sacred Heart, A. Savoia Hospital, infectiuos diseases, Università degli studi di Torino (UNITO), Modena University Hospital, L. Sacco University Hospital, Ancona University Hospital, Grosseto General Hospital, Institute of Infectious Diseases, Sacro Cuore Catholic University, Infectious Diseases Unit, University Hospital of Siena, Prosperi, M, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, M, Bagnarelli, P, Carli, T, De Luca, A, Mancuso, S, Prosperi MC, Zazzi M, Punzi G, Monno L, Colao G, Corsi P, Di Giambenedetto S, Meini G, Ghisetti V, Bonora S, Pecorari M, Gismondo MR, Bagnarelli P, Carli T, De Luca A, ARCA Collaborative Group [.., Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Maggiolo F, Callegaro A, Calza L, Re MC, Raffaele P, Turconi P, Mandas A, Tini S, Zoncada A, Paolini E, Amadio G, Sighinolfi L, and ]

Subjects
Male, Lopinavir/ritonavir, HIV Infections, boosted protease inhibitor, Lopinavir, Cohort Studies, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, virologic failure, HIV Infection, Treatment Failure, 030212 general & internal medicine, Pyrimidinone, 0303 health sciences, education.field_of_study, lopinavir/ritonavir, Viral Load, Resistance mutation, first-line antiretroviral therapy, Reverse Transcriptase Inhibitor, 3. Good health, Treatment Outcome, Infectious Diseases, RNA, Viral, Reverse Transcriptase Inhibitors, Medicine, Drug Therapy, Combination, Female, Survival Analysi, Viral load, Human, medicine.drug, Anti-HIV Agents, Population, Pyrimidinones, Settore MED/17 - MALATTIE INFETTIVE, Emtricitabine, human immunodeficiency virus type 1, 03 medical and health sciences, Virology, Drug Resistance, Viral, antiretroviral drug resistance, medicine, Humans, Protease inhibitor (pharmacology), education, HIV Protease Inhibitor, Ritonavir, 030306 microbiology, business.industry, Anti-HIV Agent, HIV Protease Inhibitors, Survival Analysis, HIV-1, Cohort Studie, business
Abstract

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.

Published
2010
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10. Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naïve and pretreated patients

Author

Saladini, F, Meini, G, Bianco, C, Monno, L, Punzi, G, Pecorari, M, Borghi, V, Di Pietro, M, Filice, G, Gismondo, Mr, Micheli, V, Penco, G, Carli, T, De Luca, A, Zazzi, M, Consolini, Rita, for the ARCA Collaborative Group, and Consolini, R.

Subjects
Microbiology (medical), Pyridones, Integrase inhibitor, HIV Infections, Drug resistance, HIV Integrase, Pharmacology, medicine.disease_cause, Piperazines, 03 medical and health sciences, chemistry.chemical_compound, In vivo, Raltegravir Potassium, Drug Resistance, Viral, Oxazines, medicine, Humans, HIV Integrase Inhibitors, 030304 developmental biology, 0303 health sciences, Mutation, drug resistance, biology, human immunodeficiency virus, 030306 microbiology, General Medicine, Raltegravir, Virology, Pyrrolidinones, 3. Good health, Integrase, Regimen, Infectious Diseases, chemistry, Dolutegravir, biology.protein, HIV-1, Heterocyclic Compounds, 3-Ring, medicine.drug
Abstract

The prevalence of HIV-1 integrase mutations related to resistance to the next-generation integrase inhibitor (INI), dolutegravir (DTG), was assessed in 440 INI-naïve subjects and in 120 patients failing a raltegravir (RTG)-containing regimen. Of the mutations selected by DTG in vitro, S153FY was not detected in any isolate while L101I and T124A were highly prevalent in both groups and significantly associated with non-B subtype. RTG-selected double and triple mutants, mostly the G140S/Q148H variant, were detected in only 32 (26.7%) RTG-treated patients. As L101I and T124A do not appear to exert any major effect in vivo and double and triple mutants resistant to DTG are infrequently selected by RTG, DTG can be effectively used in INI-naïve patients and may retain activity in many patients failing RTG.

Published
2012

11. Evolution of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy from 2000 to 2010

Author

Colafigli, M, Torti, C, Trecarichi, Em, Albini, L, Rosi, A, Micheli, V, Manca, N, Penco, G, Bruzzone, B, Punzi, G, Corsi, P, Parruti, G, Bagnarelli, P, Monno, L, Gonnelli, A, Cauda, R, Di Giambenedetto, S, Arca, Ucsc, CollaboratorsFabbiani M, Brescia HIV resistance study g. r. o. u. p. s., Sidella, L, Mondi, A, Farina, S, D'Avino, A, Fanti, I, Doino, M, Prosperi, M, Gargiulo, F, Benini, A, Paraninfo, G, Quiros Roldan, E, Castelnuovo, F, Carosi, G, Scalzini, A, Castelli, F, Giacometti, A, Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Carla, M, Pristera, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Palvarini, L, Almi, P, Todaro, G, Gianotti, N, Cicconi, P, Rusconi, S, Gismondo, Mr, Biondi, Ml, Capetti, A, Meraviglia, P, Boeri, E, Pecorari, M, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, Sm, Filice, G, Baldanti, F, Francisci, D, Polilli, E, Sacchini, D, Martinelli, C, and Consolini, Rita

Published
2012

12. A novel methodology for large-scale phylogeny partition

Author

Prosperi, Mc, Ciccozzi, M, Fanti, I, Saladini, F, Pecorari, M, Borghi, V, Di Giambenedetto, S, Bruzzone, B, Capetti, A, Vivarelli, A, Rusconi, S, Re, Mc, Gismondo, Mr, Sighinolfi, L, Gray, Rr, Salemi, M, Zazzi, M, De Luca, A, CollaboratorsGiacometti A, ARCA collaborative g. r. o. u. p., Butini, L, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Micheli, V, Biondi, Ml, Gianotti, N, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, and Consolini, Rita

Published
2011

13. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mc1, Mackie, N, Di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, Fm, Van Laethem, K, Bansi, L, van de Vijver DA, Geretti, Am, De Luca, A, Giacometti A, SEHERE c. o. n. s. o. r. t. i. u. m., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Carla Re, M, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, d'Arminio Monforte, A, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Bello, Fd, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Fadda, G, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, Pd, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E, Lengauer, T, Däumer, M, Hoffmann, D, Schülter, E, Müller, C, Oette, M, Reuter, S, Esser, S, Fätkenheuer, G, Rockstroh, J, Incardona, F, Rosen Zvi, M, Clotet, B, Thalme, A, Svedhem, V, Bratt, G, Gargiulo, F, Lapadula, G, Manca, N, Paraninfo, G, Quiros Roldan, E, Carosi, G, Castelnuovo, F, Vandamme, Am, Van Wijngaerden, E, Ainsworth, J, Anderson, J, Babiker, A, Dunn, D, Easterbrook, P, Fisher, M, Gazzard, B, Garrett, N, Gilson, R, Gompels, M, Hill, T, Johnson, M, Leen, C, Orkin, C, Phillips, A, Pillay, D, Porter, K, Post, F, Sabin, C, Sadiq, T, Schwenk, A, Walsh, J, Delpech, V, Palfreeman, A, Glabay, A, Lynch, J, Hand, J, de Souza, C, Perry, N, Tilbury, S, Churchill, D, Nelson, M, Waxman, M, Mandalia, S, Kall, M, Korat, H, Taylor, C, Ibrahim, F, Campbell, L, James, L, Brima, N, Williams, I, Youle, M, Lampe, F, Smith, C, Grabowska, H, Chaloner, C, Puradiredja, Di, Weber, J, Ramzan, F, Carder, M, Wilson, A, Dooley, D, Asboe, D, Pozniak, A, Cameron, S, Cane, P, Chadwick, D, Clark, D, Collins, S, Lazarus, L, Dolling, D, Fearnhill, E, Castro, H, Coughlin, K, Zuckerman, M, Booth, C, Goldberg, D, Hale, A, Kaye, S, Kellam, P, Leigh Brown, A, Smit, E, Templeton, K, Tilston, P, Tong, W, Zhang, H, Ushiro Lumb, I, Oliver, T, Bibby, D, Mitchell, S, Mbisa, T, Wildfire, A, Tandy, R, Shepherd, J, Maclean, A, Bennett, D, Hopkins, M, Garcia Diaz, A, Kirk, S, Sloot, P. M., Virology, Prosperi, M, Mackie, N, di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, F, van laethem, K, Bansi, L, van de Vijver, D, Geretti, A, de luca, A, and Mancuso, S

Subjects
Male, Drug Resistance, HIV Infections, Drug resistance, Cohort Studies, 0302 clinical medicine, Genotype, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Viral, 0303 health sciences, Proteolytic enzymes, Genotypic testing, HIV, Viral load, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Europe, Female, HIV-1, Humans, RNA, Viral, Viral Proteins, Drug Resistance, Viral, Mutation, Missense, Viral Load, Pharmacology, Infectious Diseases, 3. Good health, Cohort, Cohort study, Human, Microbiology (medical), Biology, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Viral Protein, 030306 microbiology, Anti-HIV Agent, Virology, Reverse transcriptase, Regimen, genotypic testing, viral load, Immunology, Mutation, RNA, Missense, Cohort Studie
Abstract

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load

Published
2011

14. A prognostic model for estimating the time to virologic failure in HIV-1 infected patients undergoing a new combination antiretroviral therapy regimen

Author

Prosperi, Mc, Di Giambenedetto, S, Fanti, I, Meini, G, Bruzzone, B, Callegaro, A, Penco, G, Bagnarelli, P, Micheli, V, Paolini, E, Di Biagio, A, Ghisetti, V, Di Pietro, M, Zazzi, M, De Luca, A, CollaboratorsGiacometti A, ARCA c. o. h. o. r. t., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Potenza, D, Mandas, A, Tini, S, Zoncada, A, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Bartalesi, F, Colao, G, Tosti, A, Setti, M, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Gianotti, N, Cicconi, P, Rusconi, S, Gismondo, Mr, Biondi, Ml, Capetti, A, Meraviglia, P, Boeri, E, Pecorari, M, Soria, A, Vecchi, L, Mussini, C, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, and Consolini, Rita

Published
2011

15. Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice

Author

Prosperi, Mc1, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, Mr, Bagnarelli, P, Carli, T, De Luca, A, Collaborators Giacometti A, ARCA Collaborative G. r. o. u. p., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Raffaele, P, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, Ad, Cicconi, P, Rusconi, S, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, and Lattuada, E.

Published
2010

16. Rules-based HIV-1 genotypic resistance interpretation systems predict 8 week and 24 week virological antiretroviral treatment outcome and benefit from drug potency weighting

Author

Zazzi, M, Prosperi, M, Vicenti, I, Di Giambenedetto, S, Callegaro, A, Bruzzone, B, Baldanti, F, Gonnelli, A, Boeri, E, Paolini, E, Rusconi, S, Giacometti, A, Maggiolo, F, Menzo, S, De Luca, A, ARCA Collaborative Group, Butini, L, del Gobbo, R, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Mussini, C, Pecorari, M, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, Zazzi, M, Prosperi, M, Vicenti, I, Di Giambenedetto, S, Callegaro, A, Bruzzone, B, Baldanti, F, Gonnelli, A, Boeri, E, Paolini, E, Rusconi, S, Giacometti, A, Maggiolo, F, Menzo, S, De Luca, A, Mancuso, S, Zazzi M, Prosperi M, Vicenti I, Di Giambenedetto S, Callegaro A, Bruzzone B, Baldanti F, Gonnelli A, Boeri E, Paolini E, Rusconi S, Giacometti A, Maggiolo F, Menzo S, De Luca A, ARCA Collaborative Group: [.., Butini L, del Gobbo R, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Calza L, Re M C, Pristerà R, Turconi P, Mandas A, Tini S, and ]

Subjects
Male, interpretation system, HIV Infections, Drug resistance, Logistic regression, Retrospective Studie, HIV Infection, Pharmacology (medical), Microbial Sensitivity Test, Middle Aged, Prognosis, genotype, drug resistance, algorithm, Algorithm, Treatment Outcome, Infectious Diseases, Italy, RNA, Viral, Female, Cohort study, Human, Microbiology (medical), Adult, medicine.medical_specialty, Genotype, Logistic Model, Anti-HIV Agents, Prognosi, antiretroviral, Microbial Sensitivity Tests, Internal medicine, medicine, Potency, Animals, Humans, Retrospective Studies, Pharmacology, Receiver operating characteristic, business.industry, Animal, Anti-HIV Agent, Retrospective cohort study, Odds ratio, genotype, drug potency weighting, Weighting, Logistic Models, ROC Curve, Immunology, HIV-1, business
Abstract

Objectives: To test retrospectively the ability of four freely available rules-based expert systems to predict short- and medium-term virological outcome following an antiretroviral treatment switch in pre-treated HIV-1 patients. Methods: The HIV-1 genotype interpretation systems (GISs) HIVdb, ANRS, Rega and AntiRetroScan were tested for their accuracy in predicting response to highly active antiretroviral therapy using 8 week (n = 765) and 24 week (n = 634) follow-up standardized treatment change episodes extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) database. A genotypic sensitivity score (GSS) was derived for each genotype-treatment pair for the different GISs and tested as a predictor of virological treatment outcome by univariable and multivariable logistic regression as well as by receiver operating characteristic curve analysis. The two systems implementing drug potency weights (AntiRetroScan and Rega) were evaluated with and without this correction factor. Results: All four GSSs were strong predictors of virological treatment outcome at both 8 and 24 weeks after adjusting for baseline viro-immunological parameters and previous drug exposure (odds ratios ranging from 2.04 to 2.43 per 1 unit GSS increase; P < 0.001 for all the systems). The accuracy of AntiRetroScan and Rega was significantly increased by drug potency weighting with respect to the unweighted versions (P ≤ 0.001). HIVdb and ANRS also increased their performance with the same drug potency weighting adopted by AntiRetroScan and Rega, respectively (P < 0.001 for both analyses). Conclusions: Currently available GISs are valuable tools for assisting antiretroviral treatment choices. Drug potency weighting can increase the accuracy of all systems. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Published
2009

18. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

Author

PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, CALZA, LEONARDO, RE, MARIA CARLA, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Prosperi, M, Di Giambenedetto, S, Fanti, I, Meini, G, Bruzzone, B, Callegaro, A, Penco, G, Bagnarelli, P, Micheli, V, Paolini, E, Di Biagio, A, Ghisetti, V, Di Pietro, M, Zazzi, M, De Luca, A, and Mancuso, S

Subjects
Oncology, Male, Adult, Anti-HIV Agents, Cohort Studies, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Middle Aged, Proportional Hazards Models, Treatment Failure, Viral Load, 0302 clinical medicine, ANTIRETROVIRAL THERAPY, Medicine, HIV Infection, 030212 general & internal medicine, 0303 health sciences, Health Policy, 3. Good health, Computer Science Applications, Censoring (clinical trials), Cohort, Combination, lcsh:R858-859.7, Viral load, Human, Research Article, Cart, medicine.medical_specialty, antiretroviral therapy, Health Informatics, Settore MED/17 - MALATTIE INFETTIVE, lcsh:Computer applications to medicine. Medical informatics, 03 medical and health sciences, Drug Therapy, Internal medicine, Survival analysis, 030306 microbiology, business.industry, Proportional hazards model, ANTIRETROVIRAL DRUGS, Anti-HIV Agent, HIV, GENOTYPES, Discontinuation, Regimen, Immunology, Proportional Hazards Model, Cohort Studie, business
Abstract

Background HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

Published
2011
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19. A novel methodology for large-scale phylogeny partition

Author

Prosperi, Mcf, Ciccozzi, M, Fanti, Iuri, Saladini, F, Pecorari, Mauro, Borghi, Vando, Di Giambenedetto, Simona, Bruzzone, B, Capetti, A, Vivarelli, A, Rusconi, S, Re, Mc, Gismondo, Mr, Sighinolfi, L, Gray, Rr, Salemi, M, Zazzi, M, De Luca, Andrea, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), De Luca, Andrea (ORCID:0000-0002-8311-6935), Prosperi, Mcf, Ciccozzi, M, Fanti, Iuri, Saladini, F, Pecorari, Mauro, Borghi, Vando, Di Giambenedetto, Simona, Bruzzone, B, Capetti, A, Vivarelli, A, Rusconi, S, Re, Mc, Gismondo, Mr, Sighinolfi, L, Gray, Rr, Salemi, M, Zazzi, M, De Luca, Andrea, Di Giambenedetto, Simona (ORCID:0000-0001-6990-5076), and De Luca, Andrea (ORCID:0000-0002-8311-6935)

Abstract

Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny of 11,541 human immunodeficiency virus-1 subtype B pol gene sequences from a large Italian cohort. Molecular transmission chains were characterized by means of different clinical/demographic factors, such as the interaction between male homosexuals and male heterosexuals. Our method takes an advantage of a flexible notion of transmission cluster and can become a general framework to analyse other epidemics.

Published
2011

21. [A microbiological evaluation of the use of roxithromycin in oral odontogenic infections]

Author

Am, Lo Bue, Chisari G, Salvatore Caruso, and Gismondo MR

Subjects
Adult, Bacteria, Aerobic, Bacteria, Anaerobic, Roxithromycin, Adolescent, Focal Infection, Dental, Drug Evaluation, Humans, Bacterial Infections, Microbial Sensitivity Tests, Middle Aged, Mouth Diseases
Abstract

Odontogenic infections are the primary infections caused by indigenous oral bacteria, when a factor changes their perfect equilibrium. We studied 30 samples from patients with odontogenic infections that were submitted to therapy with roxithromycin. Our results showed that 79% of aerobic and 71% of anaerobic bacteria, responsible for odontogenic infections, were sensitive to roxithromycin.

Published
1993

44. Activity of a Lactobacillus acidophilus-based douche for the treatment of bacterial vaginosis.

Author

Drago L, Vecchi E, Nicola L, Zucchetti E, Gismondo MR, and Vicariotto F

Abstract

Objectives: Bacterial vaginosis is characterized by alteration of the normal vaginal microflora, in which a mixed anaerobic bacterial flora becomes prevalent over the population of lacobacilli. Because administration of probiotics might be of some utility in restoring a normal flora, the present study aimed to evaluate the effect of a Lactobacillus acidophilus-strain-based douche on the vaginal environment in bacterial vaginosis. Patients and methods: In an open-label pilot evaluation, 40 women with bacterial vaginosis as defined by Amsel's criteria were treated for 6 days with a douche containing L. acidophilus. Vaginal smears were collected from the patients and analyzed according to Nugent's criteria at the time of diagnosis, after 6 days of treatment, and again at 20 days after the last treatment. At the same times, determination of vaginal pH and a Whiff test were performed. Results: The Nugent score decreased significantly from bacterial vaginosis or an intermediate flora toward a normal flora during treatment, and remained low during the follow-up period for almost all of the patients, indicating bacterial vaginosis in 52.5% and in 7.5% of the patients before treatment and at follow-up, respectively. After treatment, significant decreases in vaginal pH were observed, to less than pH 4.5 in 34/40 women, and the odor test became negative in all of the patients. Conclusions: In this preliminary study, treatment of bacterial vaginosis with a vaginal douche containing a strain of L. acidophilus contributed to the restoration of a normal vaginal environment. [ABSTRACT FROM AUTHOR]

Published
2007
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