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125 results on '"Perno, Carlo F."'

1. Bictegravir/emtricitabine/tenofovir alafenamide ensures high rates of virological suppression maintenance despite previous resistance in PLWH who optimize treatment in clinical practice

Author

Armenia, Daniele, Forbici, Federica, Bertoli, Ada, Berno, Giulia, Malagnino, Vincenzo, Gagliardini, Roberta, Borghi, Vanni, Gennari, William, Cicalini, Stefania, Buonomini, Annarita, Teti, Elisabetta, Lanini, Simone, Latini, Alessandra, Sarmati, Loredana, Mussini, Cristina, Andreoni, Massimo, Antinori, Andrea, Perno, Carlo F., Ceccherini-Silberstein, Francesca, and Santoro, Maria M.

Published
2022
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2. Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure.

Author

Orkin, Chloe, Schapiro, Jonathan M, Perno, Carlo F, Kuritzkes, Daniel R, Patel, Parul, DeMoor, Rebecca, Dorey, David, Wang, Yongwei, Han, Kelong, Eygen, Veerle Van, Crauwels, Herta, Ford, Susan L, Latham, Christine L, Clair, Marty St., Polli, Joseph W, Vanveggel, Simon, Vandermeulen, Kati, D'Amico, Ronald, Garges, Harmony P, and Zolopa, Andrew

Subjects
HIV infections, COMBINATION drug therapy, GENETIC mutation, PATIENT selection, VIRAL load, MULTIVARIATE analysis, REVERSE transcriptase inhibitors, RILPIVIRINE, ANTIRETROVIRAL agents, DISEASE incidence, TREATMENT failure, RISK assessment, FACTOR analysis, DESCRIPTIVE statistics, RESEARCH funding, PREDICTION models, BODY mass index, HIV, THERAPEUTICS, EVALUATION
Abstract

Background Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilpivirine long-acting (CAB + RPV LA) were expanded to include data beyond week 48, additional covariates, and additional participants. Methods Pooled data from 1651 participants were used to explore dosing regimen (every 4 or every 8 weeks), demographic, viral, and pharmacokinetic covariates as potential predictors of CVF. Prior dosing regimen experience was accounted for using 2 populations. Two models were conducted in each population—baseline factor analyses exploring factors known at baseline and multivariable analyses exploring baseline factors plus postbaseline model-predicted CAB/RPV trough concentrations (4 and 44 weeks postinjection). Retained factors were evaluated to understand their contribution to CVF (alone or in combination). Results Overall, 1.4% (n = 23/1651) of participants had CVF through 152 weeks. The presence of RPV resistance-associated mutations, human immunodeficiency virus-1 subtype A6/A1, and body mass index ≥30 kg/m2 were associated with an increased risk of CVF (P <.05 adjusted incidence rate ratio), with participants with ≥2 of these baseline factors having a higher risk of CVF. Lower model-predicted CAB/RPV troughs were additional factors retained for multivariable analyses. Conclusions The presence of ≥2 baseline factors (RPV resistance-associated mutations, A6/A1 subtype, and/or body mass index ≥30 kg/m2) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (≤first quartile) did not improve the prediction of CVF beyond the presence of a combination of ≥2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA. [ABSTRACT FROM AUTHOR]

Published
2023
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5. CMV seroprevalence and coronary CMV-DNA detection in immunocompetent patients with heart diseases

Author

CENTO, Valeria, primary, COLAGROSSI, Luna, additional, BOSSI, Irene, additional, ARMENIA, Daniele, additional, NAVA, Alice, additional, PICCINELLI, Enrico, additional, MALOBERTI, Alessandro, additional, INGLESE, Elvira, additional, MATARAZZO, Elisa, additional, DI RUSCIO, Federica, additional, PABA, Pierpaolo, additional, MARCUCCILLI, Fabbio, additional, PERRONE, Marco, additional, CHIRICOLO, Gaetano, additional, ALTERI, Claudia, additional, SCAGLIONE, Francesco, additional, VISMARA, Chiara, additional, CAMPISI, Daniela A., additional, FANTI, Diana, additional, ROMEO, Francesco, additional, ANDREONI, Massimo, additional, OLIVA, Fabrizio, additional, CECCHERINI-SILBERSTEIN, Francesca, additional, GIANNATTASIO, Cristina, additional, and PERNO, Carlo F., additional

Published
2022
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6. Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

Author

Colagrossi, Luna, Hermans, Lucas E., Salpini, Romina, Di Carlo, Domenico, Pas, Suzan D., Alvarez, Marta, Ben-Ari, Ziv, Boland, Greet, Bruzzone, Bianca, Coppola, Nicola, Seguin-Devaux, Carole, Dyda, Tomasz, Garcia, Federico, Kaiser, Rolf, Köse, Sukran, Krarup, Henrik, Lazarevic, Ivana, Lunar, Maja M., Maylin, Sarah, Micheli, Valeria, Mor, Orna, Paraschiv, Simona, Paraskevis, Dimitros, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Simon, François, Stanojevic, Maja, Stene-Johansen, Kathrine, Tihic, Nijaz, Trimoulet, Pascale, Verheyen, Jens, Vince, Adriana, Lepej, Snjezana Zidovec, Weis, Nina, Yalcinkaya, Tülay, Boucher, Charles A. B., Wensing, Annemarie M. J., Perno, Carlo F., Svicher, Valentina, and on behalf of the HEPVIR working group of the European Society for translational antiviral research (ESAR)

Published
2018
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8. Prevalence and outcome of patients with acute myocarditis and positive viral search on nasopharyngeal swab

Author

Ammirati, Enrico, primary, Varrenti, Marisa, additional, Veronese, Giacomo, additional, Fanti, Diana, additional, Nava, Alice, additional, Cipriani, Manlio, additional, Pedrotti, Patrizia, additional, Garascia, Andrea, additional, Bottiroli, Maurizio, additional, Oliva, Fabrizio, additional, Bramerio, Manuela, additional, Veronese, Silvio, additional, Giannattasio, Cristina, additional, Bonoldi, Emanuela, additional, Perno, Carlo F., additional, Camici, Paolo G., additional, and Frigerio, Maria, additional

Published
2021
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9. Secondary Mutations in the Protease Region of Human Immunodeficiency Virus and Virologic Failure in Drug-Naive Patients Treated with Protease Inhibitor-Based Therapy

Author

Italian Cohort Naive Antiretroviral (I.CO.N.A.) Study Group, Perno, Carlo F., Cozzi-Lepri, Alessandro, Balotta, Claudia, Forbici, Federica, Violin, Michela, Bertoli, Ada, Facchi, Guido, Pezzotti, Patrizio, Cadeo, Gianpiero, Tositti, Giulio, Pasquinucci, Sandro, Pauluzzi, Sergio, Scalzini, Alfredo, Salassa, Bernardino, Vincenti, Antonella, Phillips, Andrew N., Dianzani, Ferdinando, Appice, Amelia, Angarano, Gioacchino, Monno, Laura, Ippolito, Giuseppe, Moroni, Mauro, and Monforte, Antonella d'Arminio

Published
2001

10. Lower prevalence of drug resistance mutations at first-line virological failure to first-line therapy with atripla vs. tenofovir + emtricitabine/lamivudine + efavirenz administered on a multiple tablet therapy

Author

Blanco, José L., Montaner, Julio S.G., Marconi, Vincent C., Santoro, Maria M., Campos-Loza, Ariel E., Shafer, Robert W., Miller, Michael D., Paredes, Roger, Harrigan, Richard, Nguyen, Mihn L., Perno, Carlo F., Gonzalez-Hernandez, Lucero A., and Gatell, José M.

Published
2014
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11. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis

Author

Cutrell, Amy G., primary, Schapiro, Jonathan M., additional, Perno, Carlo F., additional, Kuritzkes, Daniel R., additional, Quercia, Romina, additional, Patel, Parul, additional, Polli, Joseph W., additional, Dorey, David, additional, Wang, Yongwei, additional, Wu, Sterling, additional, Van Eygen, Veerle, additional, Crauwels, Herta, additional, Ford, Susan L., additional, Baker, Mark, additional, Talarico, Christine L., additional, Clair, Marty St, additional, Jeffrey, Jerry, additional, White, C. Thomas, additional, Vanveggel, Simon, additional, Vandermeulen, Kati, additional, Margolis, David A., additional, Aboud, Michael, additional, Spreen, William R., additional, and van Lunzen, Jan, additional

Published
2021
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15. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies

Author

Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio Maria, Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxì, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini Silberstein, Francesca, Mariani, R., Iapadre, N., Grimaldi, A., Cozzolongo, R., Andreone, P., Verucchi, G., Menzaghi, B., Quirino, T., Pisani, V., Torti, MARIA CHIARA, Vecchiet, J., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L. A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, Miriam, Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Magni, C. F., Mancon, A., Monico, S., Niero, F., Russo, M. L., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Gaeta, G. B., Lembo, V., Sangiovanni, V., Di Marco, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Aragri, M., Baiocchi, L., Barbaliscia, S., Biliotti, Elisa, Biolato, M., Carioti, L., Ceccherini Silberstein, F., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Maio, V. C., Di Paolo, D., Furlan, Caterina, Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lenci, I., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, Donatella, Pellicelli, A., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M. C., Spaziante, M., Svicher, V., Tisone, G., Vespasiani Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M. S., Falconi, L., Di Giammartino, D., Di Maio, V., Cento, V., Lenci, I., Aragri, M., Rossi, P., Barbaliscia, S., Melis, M., Verucchi, G., Magni, C., Teti, E., Bertoli, A., Antonucci, F., Bellocchi, M., Micheli, V., Masetti, C., Landonio, S., Francioso, S., Santopaolo, F., Pellicelli, A., Calvaruso, V., Gianserra, L., Siciliano, M., Romagnoli, D., Cozzolongo, R., Grieco, A., Vecchiet, J., Morisco, F., Merli, M., Brancaccio, G., Di Biagio, A., Loggi, E., Mastroianni, C., Pace Palitti, V., Tarquini, P., Puoti, M., Taliani, G., Sarmati, L., Picciotto, A., Vullo, V., Caporaso, N., Paoloni, M., Pasquazzi, C., Rizzardini, G., Parruti, G., Craxã¬, A., Babudieri, S., Andreoni, M., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Iapadre, N., Grimaldi, A., Andreone, P., Menzaghi, B., Quirino, T., Pisani, V., Torti, C., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Mancon, A., Monico, S., Niero, F., Russo, M., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Gaeta, G., Lembo, V., Sangiovanni, V., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Paolo, D., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, D., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Tisone, G., Vespasiani-Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M., Falconi, L., Di Giammartino, D., Di Maio, V, Cento, V, Lenci, I, Aragri, M, Rossi, P, Barbaliscia, S, Melis, M, Verucchi, G, Magni, C, Teti, E, Bertoli, A, Antonucci, F, Bellocchi, M, Micheli, V, Masetti, C, Landonio, S, Francioso, S, Santopaolo, F, Pellicelli, A, Calvaruso, V, Gianserra, L, Siciliano, M, Romagnoli, D, Cozzolongo, R, Grieco, A, Morisco, F, Merli, M, Brancaccio, G, Di Biagio, A, Loggi, E, Mastroianni, C, Pace Palitti, V, Tarquini, P, Puoti, M, Taliani, G, Sarmati, L, Picciotto, A, Vullo, V, Caporaso, N, Paoloni, M, Pasquazzi, C, Rizzardini, G, Parruti, G, Craxì, A, Babudieri, S, Andreoni, M, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Velia C. Di Maio, Valeria Cento, Ilaria Lenci, Marianna Aragri, Piera Rossi, Silvia Barbaliscia, Michela Meli, Gabriella Verucchi, Carlo F. Magni, Elisabetta Teti, Ada Bertoli, Francesco Paolo Antonucci, Maria C. Bellocchi, Valeria Micheli, Chiara Masetti, Simona Landonio, Simona Francioso, Francesco Santopaolo, Adriano M. Pellicelli, Vincenza Calvaruso, Laura Gianserra, Massimo Siciliano, Dante Romagnoli, Raffaele Cozzolongo, Antonio Grieco, Jacopo Vecchiet, Filomena Morisco, Manuela Merli, Giuseppina Brancaccio, Antonio Di Biagio, Elisabetta Loggi, Claudio M. Mastroianni, Valeria Pace Palitti, Pierluigi Tarquini, Massimo Puoti, Gloria Taliani, Loredana Sarmati, Antonino Picciotto, Vincenzo Vullo, Nicola Caporaso, Maurizio Paoloni, Caterina Pasquazzi, Giuliano Rizzardini, Giustino Parruti, Antonio Craxì, Sergio Babudieri, Massimo Andreoni, Mario Angelico, Carlo F. Perno, Francesca Ceccherini-Silberstein, for the HCV Italian Resistance Network Study Group: [.., P. Andreone, E. Loggi, G. Verucchi, ], Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio M., Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxã¬, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini-Silberstein, Francesca, Nicolini, L. A., Magni, C. F., Russo, M. L., Gaeta, G. B., Di Marco, V., Di Maio, V. C., Sorbo, M. C., Mura, M. S., Di Maio, Velia C, Magni, Carlo F, Bellocchi, Maria C, Pellicelli, Adriano M, Mastroianni, Claudio M, Craxì, Antonio, Perno, Carlo F, and Ceccherini Silberstein, Francesca

Subjects
Male, 0301 basic medicine, hepatitis C virus, Sustained Virologic Response, Sofosbuvir, Hepacivirus, Drug Resistance, resistance-associated substitutions, Viral Nonstructural Proteins, VARIANTS, NS5A, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, INFECTION, antiviral therapy, Medicine, hepatitis C viru, Viral, Treatment Failure, Chronic, direct-acting antivirals, resistance test, hepatology, biology, GENOTYPE 1, virus diseases, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Hepatitis C, Italy, Combination, Interferon, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Author Keywords:antiviral therapy, RIBAVIRIN, Sequence Analysis, Human, medicine.drug, medicine.medical_specialty, Daclatasvir, Genotype, Hepatitis C virus, Antiviral Agents, LONG-TERM PERSISTENCE, DACLATASVIR, 03 medical and health sciences, Drug Therapy, Aged, Drug Resistance, Viral, Hepatitis C, Chronic, Humans, Interferons, Mutation, Ribavirin, Sequence Analysis, DNA, Hepatology, TREATMENT-NAIVE, Internal medicine, Antiviral Agent, resistance-associated substitution, direct-acting antiviral, Hepaciviru, resistance test KeyWords Plus:HEPATITIS-C VIRUS, business.industry, Viral Nonstructural Protein, DNA, biology.organism_classification, Clinical trial, 030104 developmental biology, SOFOSBUVIR, chemistry, Sequence Analysi, Immunology, business
Abstract

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

Published
2017

17. Influence of glomerular function on values of cardiac troponin T in patients with suspected acute coronary syndrome

Author

Bussetti, Marco, primary, Roccaforte, Vincenzo, additional, Buonocore, Ruggero, additional, Cappellini, Fabrizio, additional, Liuzzi, Giammaria, additional, Daves, Massimo, additional, Cemin, Roberto, additional, Burati, Silvia, additional, Tosca, Marta C., additional, Russo, Rosalba M., additional, De Angelis, Maria L., additional, Porreca, Wanda P., additional, Perno, Carlo F., additional, Pastori, Stefano, additional, and Brambilla, Paolo, additional

Published
2020
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23. Secondary mutations in the protease region of Human Immunodeficiency Virus and virologic failure in drug-naive patients treated with protease inhibitor--based therapy

Author

Perno, Carlo F., Cozzi-Lepri, Alessandro, Balotta, Claudia, Forbici, Federica, Violin, Michela, Bertoli, Ada, Facchi, Guido, Pezzotti, Patrizio, Cadeo, Gianpiero, Tositti, Giulio, Pasquinucci, Sandro, Pauluzzi, Sergio, Scalzini, Alfredo, Salassa, Bernardino, Vincenti, Antonella, Phillips, Andrew N., Dianzani, Ferdinando, Appice, Amelia, Angarano, Gioacchino, Monno, Laura, Ippolito, Giuseppe, Moroni, Mauro, and Monforte, Antonella d'Arminio

Subjects
HIV infection -- Drug therapy, HIV (Viruses) -- Genetic aspects, Protease inhibitors, Health
Published
2001

24. Methotrexate inhibits SARS‐CoV‐2 virus replication "in vitro".

Author

Caruso, Arnaldo, Caccuri, Francesca, Bugatti, Antonella, Zani, Alberto, Vanoni, Marco, Bonfanti, Paolo, Cazzaniga, Marina E., Perno, Carlo F., Messa, Cristina, and Alberghina, Lilia

Subjects
SARS-CoV-2, VIRAL replication, METHOTREXATE, COVID-19 pandemic, COVID-19, REVERSE genetics
Abstract

In early 2020 the new respiratory syndrome COVID‐19 (caused by the zoonotic SARS‐CoV‐2 virus) spread like a pandemic, starting from Wuhan, China, causing severe economic depression. Despite some advances in drug treatments of medical complications in the later stages of the disease, the pandemic's death toll is tragic, as no vaccine or specific antiviral treatment is currently available. By using a systems approach, we identify the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, as a possible target. We show that methotrexate, an FDA‐approved inhibitor of purine biosynthesis, potently inhibits viral RNA replication, viral protein synthesis, and virus release. The effective antiviral methotrexate concentrations are similar to those used for established human therapies using the same drug. Methotrexate should be most effective in patients at the earliest appearance of symptoms to effectively prevent viral replication, diffusion of the infection, and possibly fatal complications. Highlights: The COVID‐19 pandemic caused by the SARS‐CoV‐2 virus is a global public health threat causing over 800000 deaths, millions of infected people, and severe economic depression.No vaccine or specific antiviral treatments are currently available.By inhibiting the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, the FDA‐approved drug methotrexate efficiently blocks SARS‐CoV‐2 replication. [ABSTRACT FROM AUTHOR]

Published
2021
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25. HCV resistance compartmentalization within tumoral and non‐tumoral liver in transplanted patients with hepatocellular carcinoma

Author

Sorbo, Maria C, primary, Carioti, Luca, additional, Bellocchi, Maria C, additional, Antonucci, FrancescoPaolo, additional, Sforza, Daniele, additional, Lenci, Ilaria, additional, Ciancio Manuelli, Matteo, additional, Armenia, Daniele, additional, De Leonardis, Francesco, additional, Milana, Martina, additional, Manzia, Tommaso M, additional, Angelico, Mario, additional, Tisone, Giuseppe, additional, Cento, Valeria, additional, Perno, Carlo F, additional, and Ceccherini‐Silberstein, Francesca, additional

Published
2019
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26. Combined evaluation of genotype and phenotype of thiopurine S-methyltransferase (TPMT) in the clinical management of patients in chronic therapy with azathioprine

Author

Rucci, Francesco, primary, Cigoli, Maria Sole, additional, Marini, Valeria, additional, Fucile, Carmen, additional, Mattioli, Francesca, additional, Robbiano, Luigi, additional, Cavallari, Ugo, additional, Scaglione, Francesco, additional, Perno, Carlo F., additional, Penco, Silvana, additional, and Marocchi, Alessandro, additional

Published
2019
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28. Current and future challenges in HCV: insights from an Italian experts panel

Author

Andreoni, Massimo, primary, Babudieri, Sergio, additional, Bruno, Savino, additional, Colombo, Massimo, additional, Zignego, Anna L., additional, Di Marco, Vito, additional, Di Perri, Giovanni, additional, Perno, Carlo F., additional, Puoti, Massimo, additional, Taliani, Gloria, additional, Villa, Erica, additional, and Craxì, Antonio, additional

Published
2017
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29. Oxidative stress and neuroAIDS: triggers, modulators and novel antioxidants

Author

Mollace, Vincenzo, Nottet, Hans S.L.M., Clayette, Pascal, Turco, Maria C., Muscoli, Carolina, Salvemini, Daniela, and Perno, Carlo F.

Subjects
Oxidation, Physiological -- Analysis, AIDS patients -- Physiological aspects, Antioxidants -- Physiological aspects, Nervous system diseases -- Physiological aspects, Health, Psychology and mental health
Abstract

Neurological disorders represent one of the most common disturbances accompanying HIV infection. In the past few years, highly antiretroviral active therapy has significantly reduced the incidence of HIV-related diseases. However, neurological dysfunction in AIDS patients still remains an unresolved problem. Oxidative stress, which occurs in brain tissues of patients undergoing HIV infection and is implicated in cell death of both astroglia and neurones, has recently been suggested to play a role in the pathogenesis of neuroAIDS. Thus, a better understanding of the processes that trigger and modulate free radical formation in brain tissues of AIDS patients might help in a successful therapeutic approach to the neuropathogenesis of HIV infection.

Published
2001

30. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

Author

Gregson, John, primary, Tang, Michele, additional, Ndembi, Nicaise, additional, Hamers, Raph L, additional, Rhee, Soo-Yon, additional, Marconi, Vincent C, additional, Diero, Lameck, additional, Brooks, Katherine A, additional, Theys, Kristof, additional, Rinke de Wit, Tobias, additional, Arruda, Monica, additional, Garcia, Frederico, additional, Monge, Susana, additional, Günthard, Huldrych F, additional, Hoffmann, Christopher J, additional, Kanki, Phyllis J, additional, Kumarasamy, Nagalingeshwaran, additional, Kerschberger, Bernard, additional, Mor, Orna, additional, Charpentier, Charlotte, additional, Todesco, Eva, additional, Rokx, Casper, additional, Gras, Luuk, additional, Helvas, Elias K, additional, Sunpath, Henry, additional, Di Carlo, Domenico, additional, Antinori, Antonio, additional, Andreoni, Massimo, additional, Latini, Alessandra, additional, Mussini, Cristina, additional, Aghokeng, Avelin, additional, Sonnerborg, Anders, additional, Neogi, Ujjwal, additional, Fessel, William J, additional, Agolory, Simon, additional, Yang, Chunfu, additional, Blanco, Jose L, additional, Juma, James M, additional, Smit, Erasmus, additional, Schmidt, Daniel, additional, Watera, Christine, additional, Asio, Juliet, additional, Kurungi, Wilford, additional, Tostevin, Anna, additional, El-Hay, Tal, additional, Clumeck, Nathan, additional, Goedhals, Dominique, additional, Van Vuuren, Cloete, additional, Bester, Philip A, additional, Sabin, Caroline, additional, Mukui, Irene, additional, Santoro, MARIA M, additional, Perno, Carlo F, additional, Hunt, Gillian, additional, Morris, Lynn, additional, Camacho, Ricardo, additional, De Oliveira, Tulio, additional, Pillay, Deenan, additional, Schulter, Eugene, additional, Murakami-Ogasawara, Akio, additional, Reyes-Terán, Gustavo, additional, Romero, Karla, additional, Avila-Rios, Santiago, additional, Sirivichayakul, Sunee, additional, Ruxrungtham, Kiat, additional, Mekprasan, Suwanna, additional, Dunn, David, additional, Kaleebu, Pontiano, additional, Raizes, Elliot, additional, Kantor, Rami, additional, Shafer, Robert W, additional, and Gupta, Ravindra K, additional

Published
2016
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31. Very High Pre-Therapy Viral Load is a Predictor of Virological Rebound in HIV-1-Infected Patients Starting a Modern First-Line Regimen

Author

Armenia, Daniele, Carlo, Domenico Di, Cozzi-Lepri, Alessandro, Calcagno, Andrea, Borghi, Vanni, Gori, Caterina, Bertoli, Ada, Gennari, William, Bellagamba, Rita, Castagna, Antonella, Latini, Alessandra, Pinnetti, Carmela, Cicalini, Stefania, Saracino, Annalisa, Lapadula, Giuseppe, Rusconi, Stefano, Castelli, Francesco, Giambenedetto, Simona Di, Andreoni, Massimo, Di Perri, Giovanni, Antinori, Andrea, Mussini, Cristina, Ceccherini-Silberstein, Francesca, Monforte, Antonella D'Arminio, Perno, Carlo F, and Santoro, Maria M

Abstract

Background Pre-cART (combined antiretroviral therapy) plasma viral load >500,000 copies/ml has been associated with a lower probability of achieving virological suppression, while few data about its role on maintenance of virological suppression are available. In this study we aimed to clarify whether high levels of pre-cART viraemia are associated with virological rebound (VR) after virological suppression.Methods HIV-infected individuals who achieved virological suppression after first-line cART were included. VR was defined as the first of two consecutive viraemia >50 copies/ml (VR50) or, in an alternative analysis, >200 copies/ml (VR200). The impact of pre-cART viraemia on the risk of VR was evaluated by survival analyses.Results Among 5,766 patients included, 59.2%, 31.4%, 5.2% and 4.2% had pre-cART viraemia =100,000, 100,001–500,000, 500,001–1,000,000 and >1,000,000 copies/ml, respectively. Patients with pre-cART viraemia levels >1,000,000 copies/ml had the highest probability of VR (>1,000,000; 500,000– 1,000,000; 100,000–500,000; <100,000 copies/ml; VR50: 28.4%; 24.3%; 17.6%; 13.8%, P<0.0001; VR200: 14.4%; 11.1%; 7.2%; 7.6%; P=0.009). By Cox multivariable analyses, patients with pre-cART viraemia >500,000 and >1,000,000 copies/ml showed a significantly higher risk of VR regardless of the VR end point used. No difference in the risk of VR was found between patients with pre-cART viraemia ranging 500,000–1,000,000 copies/ml and those with pre-cART viraemia >1,000,000 copies/ml, regardless of the VR end point used.Conclusions Pre-cART plasma viral load levels >500,000 copies/ml can identify fragile patients with poorer chance of maintaining virological control after an initial response. An effort in defining effective treatment strategies is mandatory for these patients that remain difficult to treat.

Published
2019
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32. Efficacy and safety of sofosbuvir/simeprevir plus flat dose ribavirin in genotype 1 elderly cirrhotic patients: A real-life study.

Author

Pellicelli, Adriano M., Pace Palitti, Valeria, Vignally, Pascal, Ceccherini ‐ Silberstein, Francesca, Siciliano, Massimo, Giannelli, Valerio, Moretti, Alessandra, Tarquini, Pierluigi, Scifo, Gaetano, Messina, Vincenzo, Ascione, Antonio, Izzi, Antonio, Marignani, Massimo, D'Ambrosio, Cecilia, Fondacaro, Lucia, Ettorre, Giuseppe M., Ialongo, Pasquale, Sacco, Rodolfo, Perno, Carlo F., and Barbarini, Giorgio

Subjects
SOFOSBUVIR, RIBAVIRIN, ANTIVIRAL agents, HEPATITIS C treatment, HEPATITIS C virus, TREATMENT of cirrhosis of the liver
Abstract

Background & Aims The proportion of HCV-infected patients over age 65 years in Western countries is increasing. This growth and the advent of new antiviral therapy bring into the question the real-world efficacy and safety of the combination of sofosbuvir ( SOF) and simeprevir ( SMV) plus a flat dose of 800 mg/d ribavirin ( RBV) in elderly patients with cirrhosis compared to younger patients. Methods Retrospective observational multicentre real-life investigation study of SOF/ SMV/ RBV for a duration of 12 weeks in HCV genotype 1-infected patients with cirrhosis. Results Of the 270 patients enrolled in this study, with compensated cirrhosis, 133 (49.2%) were ≥65 years of age. Sustained virological response at 12 weeks ( SVR12) was achieved by 94.2% (129/137) of those aged <65 years and 97.7% (130/133) of those ≥65 years. Diabetes was the most common comorbidity in patients ≥65 years compared to younger patients (26.3% vs 12.4% P<.003). The most common adverse event ( AE) in elderly patients was a grade 2 anaemia (35.3% vs 19.9% P<.004). Conclusions Sofosbuvir/simeprevir plus a daily flat dose of RBV 800 mg for 12 weeks was highly effective and safe in genotype 1 elderly patients with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Published
2017
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33. A Boceprevir Failure in a Patient Infected with HCV Genotype 1G: Importance and Limitations of Virus Genotyping Prior to HCV Protease-Inhibitor-Based Therapy

Author

Cento, Valeria, primary, Landonio, Simona, additional, De Luca, Francesca, additional, Maio, Velia C Di, additional, Micheli, Valeria, additional, Mirabelli, Carmen, additional, Niero, Fosca, additional, Magni, Carlo, additional, Rizzardini, Giuliano, additional, Perno, Carlo F, additional, and Ceccherini-Silberstein, Francesca, additional

Published
2013
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34. Circulation of HIV-1 CRF02_AG among MSM Population in Central Italy: A Molecular Epidemiology-Based Study

Author

Giuliani, Massimo, primary, Santoro, Maria M., additional, Lo Presti, Alessandra, additional, Cella, Eleonora, additional, Scognamiglio, Paola, additional, Lai, Alessia, additional, Latini, Alessandra, additional, Fabeni, Lavinia, additional, Gori, Caterina, additional, Pinnetti, Carmela, additional, Girardi, Enrico, additional, Perno, Carlo F., additional, Zehender, Gianguglielmo, additional, and Ciccozzi, Massimo, additional

Published
2013
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37. Cross-Resistance among Nonnucleoside Reverse Transcriptase Inhibitors Limits Recycling Efavirenz after Nevirapine Failure

Author

Antinori, Andrea, primary, Zaccarelli, Mauro, additional, Cingolani, Antonella, additional, Forbici, Federica, additional, Rizzo, Maria G., additional, Trotta, Maria P., additional, Di Giambenedetto, Simona, additional, Narciso, Pasquale, additional, Ammassari, Adriana, additional, Girardi, Enrico, additional, De Luca, Andrea, additional, and Perno, Carlo F., additional

Published
2002
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38. Lower prevalence of drug resistance mutations at first-line virological failure to first-line therapy with atripla vs. tenofoviremtricitabinelamivudineefavirenz administered on a multiple tablet therapy

Author

Blanco, José L., Montaner, Julio S.G., Marconi, Vincent C., Santoro, Maria M., Campos-Loza, Ariel E., Shafer, Robert W., Miller, Michael D., Paredes, Roger, Harrigan, Richard, Nguyen, Mihn L., Perno, Carlo F., Gonzalez-Hernandez, Lucero A., and Gatell, José M.

Abstract

Fixed-dose combination antiretroviral therapy administered as a single-tablet regimen (STR) may improve virologic suppression rates. The effect of STRs on development of resistance when virologic failure occurs on STRs is not known.

Published
2014
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39. Implications of HIV Drug Resistance on First- and Second-Line Therapies in Resource-Limited Settings: Report from a Workshop Organized by the Collaborative HIV and Anti-HIV Drug Resistance Network

Author

Pillay, Deenan, Albert, Jan, Bertagnolio, Silvia, Boucher, Charles, Brun-Vezinet, Francoise, Clotet, Bonaventura, Giaquinto, Carlo, and Perno, Carlo F

Abstract

Here, we summarize the discussions and conclusions from an expert workshop held in October 2012 to consider the implications of HIV drug resistance in the context of scale-up of access to antiretroviral therapy and prophylaxis in resource-limited settings. Topics considered during the workshop included the implications of drug resistance for the selection of first-line regimens and sequencing of treatments, optimal surveillance strategies and prevention of mother-to-child transmission.

Published
2013
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40. Interpretation of Genotypic HIV-1 Resistance to Darunavir and Virological Response: Validation of Available Systems and of a New Score

Author

De Luca, Andrea, Giambenedetto, Simona Di, Maserati, Renato, Gianotti, Nicola, Narciso, Pasquale, Antinori, Andrea, Perri, Giovanni Di, Prosperi, Mattia CF, Baldanti, Fausto, Micheli, Valeria, Zazzi, Maurizio, Perno, Carlo F, and Santoro, Maria M

Abstract

Background There is not yet consensus on interpretation of genotypic HIV-1 resistance to darunavir (DRV). We validated existing rules and a newly derived score.Methods Protease inhibitor (PI)-failing patients starting a DRV/ritonavir-based regimen, with available baseline resistance genotypes, were extracted from three Italian databases. Virological response (VR) was analysed between 4 and 32 follow-up weeks, defined as a drop from baseline HIV RNA of=2 log10or a value<50 copies/ml if the last measurement had been obtained at=12 weeks and as HIV RNA<50 copies/ml if it had been obtained at>12 weeks of follow-up. DRV/ritonavir resistance was interpreted by seven algorithms. A new weighted score (DRV-2009) was derived and validated, analysing associations of protease mutations with VR.Results A total of 217 patients were analysed, with a mean (±sd) follow-up time of 17 (±9) weeks. At baseline, median HIV RNA was 4.26 log10copies/ml (IQR 3.11-5.03); VR was achieved in 135/217 (62%) patients. Adjusting for use of a new drug class, number of previous PIs experienced, CD4+T-cell count and HIV RNA, only the Rega DRV/ritonavir interpretation was significantly associated with VR (per increase in susceptibility category, OR 1.94, 95% CI 1.32–2.86; P<0.001). The DRV-2009 score V11I+L33F+R41K+I47V+2*I-50V+2*I54M+K55R+D60E+L74P+L76V+N88D+2*L89V– L10I/V–I13V–G16E–G48V–F53I/L–I62V–I66F–V77I (<0 indicating susceptibility, 0–1 intermediate resistance and=2 resistance) correlated with VR in the derivation set (n=132, R=0.395; P<0.001). In the validation set (n=85), after adjusting for mutual interpretation and new use of enfuvirtide, DRV-2009 (P=0.017) and Rega (P=0.013) were both independently associated with VR.Conclusions In contrast to the other algorithms, both the DRV-2009 score and Rega interpretation showed a robust predictive capacity of VR to DRV/ritonavir-con-taining regimens.

Published
2011
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41. Historical resistance profile helps to predict salvage failure

Author

Zaccarelli, Mauro, Lorenzini, Patrizia, Ceccherini-Silberstein, Francesca, Tozzi, Valerio, Forbici, Federica, Gori, Caterina, Trotta, Maria P, Boumis, Evangelo, Narciso, Pasquale, Perno, Carlo F, and Antinori, Andrea

Abstract

Background This study compared the predictive value for treatment failure of extended resistance detected in the current genotype resistance test (GRT) versus those from GRT history in patients with multiple combination anti-retroviral therapy (cART) failures.Methods Patients who underwent three GRT between 1999 and 2007 were included. Extended resistance at genotypic sensitivity score (GSS) using the Rega 7.1 interpretation system compared with a non-standard definition (defined as class-wide resistance [CWR] on the basis of International AIDS Society–USA mutations) was assessed both for current and historical GRTs (a combination of mutations was detected in all three tests). The predictive role of extended resistance for treatment failure was evaluated with an adjusted Cox proportional hazard model.Results Overall, 177 patients were included. The historical GRT increased the number of patients with extended resistance to all three major drug classes by 25% in comparison with the current GRT. Using the GSS method, the absence of detection of any active drug in any drug class was predictive of failure with both the current and historical GRTs. Similarly, the number of active drugs in the cART regimen after the third resistance test, used as continuous variable, was also predictive of failure. Using both GSS approaches, current genotype had a higher effect than historical genotype on risk of treatment failure. Using the non-standard definition (CWR), historical resistance predicted failure better than current resistance.Conclusions Our results provide an epidemiological demonstration that analysis of a combined latest and historical GRT, which also considers archived mutations, might better identify of the more virologically impaired patients in order to assess the best salvage treatment.

Published
2009
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42. Use of novel antiretroviral agents in rescue regimens: A case of early virological failure to raltegravir.

Author

Tommasi, Chiara, Ceccherini-Silberstein, Francesca, D'Arrigo, Roberta, Bellagamba, Rita, Tempestilli, Massimo, Dessì, Carlo, Santoro, Maria M., Forbici, Federica, Nicastri, Emanuele, Pucillo, Leopoldo P., Perno, Carlo F., and Narciso, Pasquale

Subjects
ANTIRETROVIRAL agents, DRUG resistance, VIRUS research, HIGHLY active antiretroviral therapy
Abstract

In patients with virological failure during highly active antiretroviral therapy (HAART) and drug resistance, guidelines recommend the achievement of maximal virological suppression by the use of a new regimen with at least 2 active drugs. We describe the clinical outcome of a heavily antiretroviral-experienced patient who experienced early failure to raltegravir. [ABSTRACT FROM AUTHOR]

Published
2010
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43. Preparation and Characterization of an Intravenous Solution of IgG From Human Immunodeficiency Virus-Seropositive Donors

Author

Cummins, Larry M., Weinhold, Kent J., Matthews, Thomas J., Langlois, Alphonse J., Perno, Carlo F., Condie, Richard M., and Allain, Jean-Pierre

Abstract

An intravenous solution of 99% pure globulin (hyperimmune IgG, HIVIG) was obtained from pooled plasma of selected human immunodeficiency virus (HIV-1 (-seropositive asymptomatic donors with > 400 CD4+/μL cells per microliter and a high titer of antibody to HIV-1 p24 protein. HIVIG had high titers of antibody to p24, glycoprotein 41 (gp41), and gp 120, group-specific neutralizing activity, and binding to the gp120 hypervariable loop region. It inhibited syncytia formation. At low concentration, it enhanced viral production of HIV-1 in infected peripheral blood monocytes but was inhibitory at higher concentration. HIVIG directed group-specific antibody-dependent cellular cytotoxicity against HIV-infected targets. For a period of 6 to 28 months, plasma donors kept stable antibody titers and had a 1.0% decrease in CD4+cells per month. One gram per kilogram HIVIG injected in two juvenile chimpanzees was well tolerated and did not transmit HIV, as measured by negative cell culture, IgM immune response to HIV proteins, and polymerase chain reaction. The mean half-life of HIV-1 p24 antibody was 15 days. These preliminary data suggest that HIVIG is a safe product suitable for clinical trial in HIV-1–infected individuals.

Published
1991
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44. Recommendations for the use of hepatitis C virus protease inhibitors for the treatment of chronic hepatitis C in HIV-infected persons. A position paper of the Italian Association for the Study of Infectious and Tropical Disease

Author

Armignacco, Orlando, Andreoni, Massimo, Sagnelli, Evangelista, Puoti, Massimo, Raffaele Bruno, Gaeta, Giovanni Battista, Perno, Carlo F., Santantonio, Teresa A., Bonfanti, Paolo, Bonora, Stefano, Borderi, Marco, Castagnan, Antonella, Monforte, Antonella D. Arminio, Luca, Andrea, Grossi, Paolo, Guaraldi, Giovanni, Maggiolo, Franco, Mussini, Cristina, Sagnelli, Caterina, Tavio, Marcello, Torti, Carlo, Uberti-Foppa, Caterina, Angarano, Gioacchino, Antinori, Andrea, Carosi, Giampiero, Chirianni, Antonio, Di Perri, Giovanni, Galli, Massimo, Lazzarin, Adriano, Rizzardini, Giuliano, Taliani, Gloria, Armignacco, Orlando, Andreoni, Massimo, Sagnelli, Evangelista, Puoti, Massimo, Bruno, Raffaele, Gaeta, Giovanni Battista, Perno, Carlo F, Santantonio, Teresa A, Bonfanti, Paolo, Bonora, Stefano, Borderi, Marco, Castagna, Antonella, D'arminio Monforte, Antonella, De Luca, Andrea, Grossi, Paolo, Guaraldi, Giovanni, Maggiolo, Franco, Mussini, Cristina, Sagnelli, Caterina, Tavio, Marcello, Torti, Carlo, Uberti-foppa, Caterina, Angarano, Gioacchino, Antinori, Andrea, Carosi, Giampiero, Chirianni, Antonio, Di Perri, Giovanni, Galli, Massimo, Lazzarin, Adriano, Rizzardini, Giuliano, Taliani, Gloria, Armignacco, O, Andreoni, M, Sagnelli, E, Puoti, M, Bruno, R, Gaeta, G, Perno, C, Santantonio, T, Bonfanti, P, Bonora, S, Borderi, M, Castagna, A, d'Arminio Monforte, A, De Luca, A, Grossi, P, Guaraldi, G, Maggiolo, F, Mussini, C, Sagnelli, C, Tavio, M, Torti, C, Uberti-Foppa, C, Angarano, G, Antinori, A, Carosi, G, Chirianni, A, Di Perri, G, Galli, M, Lazzarin, A, Rizzardini, G, Taliani, G, Gaeta, Gb, Perno, Cf, Santantonio, Ta, and Taliani, G.

Subjects
Microbiology (medical), Protease Inhibitor, HIV Infections, Hepacivirus, PEG-IFN, Antiviral Agents, Coinfection, HIV-1, Hepatitis C, Chronic, Humans, Italy, Medication Reconciliation, Practice Guidelines as Topic, Protease Inhibitors, Treatment Outcome, Settore MED/17 - MALATTIE INFETTIVE, Telaprevir, Hepatitis C, Chronic, RBV, HIV Infection, Antiviral Agent, Boceprevir, Hepaciviru, HIV, Settore MED/07 - Microbiologia e Microbiologia Clinica, Antiretroviral therapy, HCV, Human
Abstract

The efficacy data obtained with boceprevir and telaprevir for persons with hepatitis C virus (HCV) genotype 1 infection raise the question of whether HCV protease inhibitors should be used in human immunodeficiency virus (HIV)/HCV co-infected persons. The Italian Association for the Study of Infectious and Tropical Diseases has made these recommendations to provide the rationale and practical indications for the use of triple anti-HCV therapy in persons living with HIV (PLWHIV). A Writing Committee of experts indicated by the President of the Association and a Consulting Committee con- tributed to the document. The final draft was submitted to the evaluation of external experts and the text modified according to their suggestions and comments. Treatment of HCV co-infection should be considered for all HCV RNA positive PLWHIV. Response-guided therapy with pegylated interferon and ribavirin is the standard treatment of PLWHIV with infection by HCV genotype 2, 3, 4, 5 and 6. Boceprevir and telaprevir should be used to treat HCV genotype 1 infection in HIV/HCV co-infected patients for 48 weeks on an individual basis, with close monitoring of their efficacy and tolerability with concur- rent antiretroviral therapy, taking into account potential drug-drug interactions. The decision to treat a patient or to wait for better treatment options, or to discontinue treatment should be made on an individual basis taking into account pre-treatment variables and the on-treatment HCV RNA kinetics.

45. Virological failures to direct acting antivirals (DAA) regimens in a real life setting show frequent resistance associated variants and may require re-treatment with unconventional strategies

Author

Di Maio, Velia Chiara, Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Barbaliscia, Silvia, Francioso, Simona, Stefania Paolucci, Melis, Michela, Verucchi, Gabriella, Coppola, Nicola, Magni, Carlo F., Santopaolo, Francesco, Landonio, Simona, Ghisetti, Valeria, Starace, Mario, D Ambrosio, Cecilia, Calvaruso, Vincenzo, Caporasol, Nicola, Pasquazzi, Caterina, Maida, Ivana, Picciotto, Antonino, Di Biagio, Antonio, Sticchi, Laura, Cozzolongo, Raffaele, Romagnoli, Dante, Biolato, Marco, Vecchiet, Jacopo, D Ettorre, Gabriella, Merli, Manuela, Gaeta, Giovanni B., Ciancio, Alessia, Marinaro, Letizia, Andreone, Pietro, Barbarini, Giorgio, Gulminetti, Roberto, Palitti, Valeria Pace, Tarquini, Perluigi, Puoti, Massimo, Sangiovanni, Vincenzo, Paoloni, Maurizio, Babudieri, Sergio, Rizzardini, Giuliano, Bruno, Savino, Andreoni, Massimo, Pellicelli, Adriano M., Parruti, Giustino, Craxi, Antonio, Angelico, Mario, Perno, Carlo F., and Ceccherini-Silberstein, Francesca

46. Natural NS3, NS5A and NS5B HCV resistance is common in real practice, differently associated to HCV genotypes and response to NS5A inhibitors

Author

Cento, Valeria, Sorbo, Maria Chiara, Bertoli, Ada, Lenci, Ilaria, Polilli, Ennio, Masetti, Chiara, Gianserra, Laura, Teti, Elisabetta, Biliotti, Elisa, Magni, Carlo F., Aragri, Marianna, Micheli, Valeria, Melis, Michela, Nicolini, Laura A., Marenco, Simona, Calvaruso, Vincenza, Stefania Paolucci, Baldanti, Fausto, Morisco, Filomena, Siciliano, Massimo, Palitti, Valeria Pace, Andreone, Pietro, Bruzzone, Bianca, Coppola, Nicola, Ruggiero, Tina, Lichtner, Miriam, Menzaghi, Barbara, Romagnoli, Dante, Iapadre, Nerio, Di Maio, Velia Chiara, Leonardis, Francesco, Milana, Martina, Cacciatore, Pierluigi, Pieri, Alessandro, Sarmati, Loredana, Landonio, Simona, Gasbarrini, Antonio, Puoti, Massimo, Craxi, Antonio, Vullo, Vincenzo, Pellicelli, Adriano M., Babudieri, Sergio, Rizzardini, Giuliano, Taliani, Gloria, Andreoni, Massimo, Pasquazzi, Caterina, Parruti, Giustino, Angelico, Mario, Perno, Carlo F., and Ceccherini-Silberstein, Francesca

48. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

Author

Gregson, J, Tang, M, Ndembi, N, Hamers, Rl, Marconi, Vc, Brooks, K, Theys, K, Arruda, M, Garcia, F, Monge, S, Kanki, Pj, Kumarasamy, N, Kerschberger, B, Mor, O, Charpentier, C, Todesco, E, Rokx, C, Gras, L, Halvas, Ek, Sunpath, H, Carlo, Dd, Antinori, A, Andreoni, M, Latini, A, Mussini, C, Aghokeng, A, Sonnerborg, A, Neogi, U, Fessel, Wj, Agolory, S, Yang, C, Blanco, Jl, Juma, Jm, Smit, E, Schmidt, D, Watera, C, Asio, J, Kirungi, W, Tostevin, A, Clumeck, N, Goedhals, D, Bester, Pa, Sabin, C, Mukui, I, Santoro, M, Perno, Cf, Hunt, G, Morris, L, Pillay, D, Schulter, E, Reyes-Teran, G, Romero, K, Avila-Rios, S, Sirivichayakul, S, Ruxrungtham, K, Mekprasan, S, Dunn, D, Kaleebu, P, Raizes, E, Kantor, R, Gupta, Rk, Rhee, S, Shafer, Rw, de Wit, Tfr, Diero, L, Camacho, R, Gunthard, Hf, Hoffmann, Cj, Di Carlo, D, El-Hay, T, van Vuuren, C, de Oliveira, T, Murakami-Ogasawara, A, [Pillay, Deenan] UCL, Dept Infect, London WC1E 6BT, England, [Gupta, Ravindra K.] UCL, Dept Infect, London WC1E 6BT, England, [Tang, Michele] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Rhee, Soo-Yon] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Shafer, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Gregson, John] London Sch Hyg & Trop Med, Dept Stat, London, England, [Ndembi, Nicaise] Inst Human Virol Nigeria, Abuja, Federal Capital, Nigeria, [Hamers, Raph L.] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1012 WX Amsterdam, Netherlands, [de Wit, Tobias F. Rinke] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1012 WX Amsterdam, Netherlands, [Hamers, Raph L.] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1012 WX Amsterdam, Netherlands, [de Wit, Tobias F. Rinke] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1012 WX Amsterdam, Netherlands, [Marconi, Vincent C.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA, [Marconi, Vincent C.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA, [Diero, Lameck] Moi Univ, Eldoret, Kenya, [Diero, Lameck] Acad Model Providing Access Healthcare, Eldoret, Kenya, [Brooks, Katherine] Brown Univ, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA, [Theys, Kristof] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Camacho, Ricardo] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Kantor, Rami] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Arruda, Monica] Univ Fed Rio de Janeiro, Inst Biol, LVM, BR-21941 Rio De Janeiro, Brazil, [Garcia, Frederico] Complejo Hosp Univ Granada, Granada, Spain, Univ Alcala de Henares, E-28871 Alcala De Henares, Spain, [Monge, Susana] CIBERESP, Madrid, Spain, [Gunthard, Huldrych F.] Univ Zurich, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland, [Gunthard, Huldrych F.] Univ Zurich, Inst Med Virol, Zurich, Switzerland, [Hoffmann, Christopher J.] Johns Hopkins Univ, Baltimore, MD USA, [Hoffmann, Christopher J.] Aurum Inst, Johannesburg, South Africa, [Kanki, Phyllis J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA, [Kumarasamy, Nagalingeshwaran] VHS, YRGCARE Med Ctr, Chennai, Tamil Nadu, India, [Kerschberger, Bernard] Med Sans Frontieres Operat Ctr Geneva, Mbabane, Eswatini, [Mor, Orna] Israel Minist Hlth, Publ Hlth Serv, Cent Virol Lab, Jerusalem, Israel, [Charpentier, Charlotte] Univ Paris Diderot, Sorbonne Paris Cite, IAME, UMR 1137, Paris, France, [Charpentier, Charlotte] INSERM, IAME, UMR 1137, Paris, France, [Charpentier, Charlotte] Hop Bichat Claude Bernard, AP HP, Virol Lab, F-75018 Paris, France, [Todesco, Eva] Hop La Pitie Salpetriere, Lab Virol, Paris, France, [Rokx, Casper] Erasmus Univ, Med Ctr, Dept Internal Med Infect Dis, Rotterdam, Netherlands, [Gras, Luuk] Stichting HIV Monitoring, Amsterdam, Netherlands, [Halvas, Elias K.] Univ Pittsburgh, Pittsburgh, PA USA, [Sunpath, Henry] Ethekwini Dist Hlth Off, Kwa Zulu, South Africa, [Di Carlo, Domenico] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy, [Santoro, Maria M.] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy, [Antinori, Antonio] INMI L Spallanzani, Infect Dis Unit, Rome, Italy, [Andreoni, Massimo] Univ Hosp Tor Vergata, Clin Infect Dis, Rome, Italy, [Latini, Alessandra] San Gallicano Dermatol Inst, HIV AIDS Unit, Rome, Italy, [Mussini, Cristina] Azienda Osped Univ Policlin, Clin Infect Dis, Modena, Italy, [Aghokeng, Avelin] Virol Lab CREMER IMPM, Yaounde, Cameroon, [Sonnerborg, Anders] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden, [Sonnerborg, Anders] Karolinska Inst, Infect Dis Unit, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Inst, Infect Dis Unit, Stockholm, Sweden, [Sonnerborg, Anders] Karolinska Univ Hosp, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Univ Hosp, Stockholm, Sweden, [Fessel, William J.] Kaiser Permanente Med Care Program Northern Calif, San Francisco, CA USA, [Agolory, Simon] Ctr Dis Control & Prevent, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Raizes, Elliot] Ctr Dis Control & Prevent, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Yang, Chunfu] Ctr Dis Control & Prevent, Int Lab Branch, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Blanco, Jose L.] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer, Clin Univ, Barcelona, Spain, [Juma, James M.] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania, [Smit, Erasmus] Publ Hlth England, Publ Hlth Lab, Birmingham, W Midlands, England, [Schmidt, Daniel] Robert Koch Inst, Dept Infect Dis Epidemiol HIV AIDS STI & Blood Bo, Berlin, Germany, [Watera, Christine] Uganda Res Unit AIDS, Entebbe, Uganda, [Asio, Juliet] Uganda Res Unit AIDS, Entebbe, Uganda, [Kaleebu, Pontiano] Uganda Res Unit AIDS, Entebbe, Uganda, [Tostevin, Anna] Minist Hlth, Kampala, Uganda, [Tostevin, Anna] UCL, MRC Clin Trials Unit, London, England, [Dunn, David] UCL, MRC Clin Trials Unit, London, England, [El-Hay, Tal] IBM Haifa Res Lab, Haifa, Israel, [Clumeck, Nathan] Univ Libre Bruxelles, St Pierre Univ Hosp, Brussels, Belgium, [Goedhals, Dominique] Univ Orange Free State, Dept Med Microbiol & Virol, Natl Hlth Lab Serv, Bloemfontein, South Africa, [van Vuuren, Cloete] Univ Orange Free State, Dept Med Microbiol & Virol, Natl Hlth Lab Serv, Bloemfontein, South Africa, [Sabin, Caroline] UCL, Infect & Populat Hlth, London, England, [Mukui, Irene] Minist Hlth, Natl AIDS & STI Control Programme, Nairobi, Kenya, [Perno, Carlo F.] INMI L Spallanzani, Antiretroviral Drugs Monitoring Unit, Rome, Italy, [Hunt, Gillian] Natl Inst Communicable Dis, Johannesburg, South Africa, [Morris, Lynn] Natl Inst Communicable Dis, Johannesburg, South Africa, [de Oliveira, Tulio] Wellcome Trust Africa Ctr Hlth & Populat Studies, Durban, South Africa, [Pillay, Deenan] Wellcome Trust Africa Ctr Hlth & Populat Studies, Durban, South Africa, [de Oliveira, Tulio] Univ KwaZulu Natal, Coll Hlth Sci, Durban, South Africa, [Schulter, Eugene] Univ Cologne, Inst Virol, D-50931 Cologne, Germany, [Murakami-Ogasawara, Akio] Natl Inst Resp Dis, Ctr Res Infect Dis, Mexico City, DF, Mexico, [Sirivichayakul, Sunee] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Ruxrungtham, Kiat] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Mekprasan, Suwanna] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Kaleebu, Pontiano] MRC UVRI Uganda Res Unit AIDS, Entebbe, Uganda, Wellcome Trust, MRC, NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, and Medical Research Council

Subjects
Cyclopropanes, Anti-HIV Agents, K65r, Drug Resistance, Antiretroviral Therapy, HIV Infections, Global Health, Settore MED/07, Virological failure, Tenofovir disoproxil fumarate, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Humans, Emtricitabine, Transmission, Highly Active, Viral, Tenofovir, Africa South of the Sahara, Benzoxazines, HIV-1, Lamivudine, Pre-Exposure Prophylaxis, Retrospective Studies, Reverse Transcriptase Inhibitors, Viral Load, Hiv-1-infected patients, virus diseases, Articles, Antiretroviral therapy, Naive patients, Alkynes, Efavirenz
Abstract

Summary Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count

Published
2016

49. Pancreatic Stone Protein in the Diagnosis of Sepsis in Children Admitted to High-Dependency Care: A Single-Center Prospective Cohort Study.

Author

Bottari G, Paionni E, Fegatelli DA, Murciano M, Rosati F, Ferrigno F, Pisani M, Cristaldi S, Musolino A, Borrelli G, Bochicchio C, Romani L, De Luca M, Agosta M, Lancella L, Villani A, Vestri A, Atti MCD, Perno CF, Porzio O, Raponi M, and Cecchetti C

Abstract

Objectives: Blood level of pancreatic stone protein (PSP) is a promising biomarker of sepsis both in adults and children. The aim of our study was to investigate the diagnostic accuracy of PSP in children with suspected sepsis and to compare diagnostic performance with other sepsis biomarkers approved for clinical use, that is, procalcitonin (PCT) and C-reactive protein (CRP)., Design: Prospective study., Setting: PICU and pediatric emergency department., Intervention: Blood levels of PSP were measured using a nanofluidic point-of-care immunoassay (abioSCOPE, Abionic SA, Switzerland) within 24 hours of admission., Measurements and Main Results: We studied 99 children aged between older than 1 month and younger than 18 years with signs and symptoms of systemic inflammatory response syndrome (irrespective of associated organ dysfunction). The prevalence of sepsis was 35 of 99 (35.4%). Patients with sepsis had higher PSP levels (p < 0.001) than patients with systemic inflammation of noninfectious cause. In this analysis, the optimal cutoff for the diagnosis of sepsis using PSP was 123 ng/mL, which resulted in a sensitivity of 0.63 (95% CI, 0.43-0.80), specificity of 0.89 (95% CI, 0.77-0.95). The PSP test area under the receiver operating characteristic curve (AUROC) was 0.82 (95% CI, 0.73-0.91) and, by comparison, procalcitonin and CRP AUROC were 0.70 (95% CI, 0.58-0.82) and 0.72 (95% CI, 0.60-0.84), respectively. Overall, the pretest to posttest probability of sepsis with a positive test changed from 0.35 to 0.73., Conclusions: In this single-center prospective pediatric cohort, admitted to the high intensive care and to the PICU, our findings suggested the potential use of PSP as a sepsis biomarker. However, because of the clinical diagnostic uncertainty with a positive result, further investigation is needed particularly in combination with other biomarkers., Competing Interests: Dr. Cecchetti received support for article research from the National Institutes of Health; he disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Published
2024
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50. CMV seroprevalence and coronary CMV-DNA detection in immunocompetent patients with heart diseases.

Author

Cento V, Colagrossi L, Bossi I, Armenia D, Nava A, Piccinelli E, Maloberti A, Inglese E, Matarazzo E, DI Ruscio F, Paba P, Marcuccilli F, Perrone M, Chiricolo G, Alteri C, Scaglione F, Vismara C, Campisi DA, Fanti D, Romeo F, Andreoni M, Oliva F, Ceccherini-Silberstein F, Giannattasio C, and Perno CF

Subjects
Female, Humans, Male, Aged, Cytomegalovirus genetics, Seroepidemiologic Studies, DNA, Immunoglobulin G, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections epidemiology, Acute Coronary Syndrome
Abstract

Background: Acute coronary syndromes (ACS) are a major cause of morbidity and mortality. As cytomegalovirus (CMV) may contribute to cardio-vascular (CV) manifestations, we sought to provide a proof-of-concept for the involvement of coronary and/or systemic CMV-reactivation as a possible ACS trigger., Methods: We prospectively enrolled consecutive patients undergoing a coronary angiography for ACS (acute-cases, N.=136), or non-ACS reasons (chronic-cases, N.=57). Matched coronary and peripheral blood-samples were processed for quantification of CMV-DNAemia (RT-PCR), CMV-IgG/IgM, and CMV-IgG avidity (ELISA). Peripheral-blood samples from 17 healthy subjects were included as controls., Results: Out of the 193 cases included, 18.1% were aged ≤55 years, 92.5% were Central-European, and 100% immunocompetent. CMV-IgG seroprevalence was 91.7% (95%CI: 87.8-95.6), significantly higher than in healthy-controls (52.9% [95%CI: 29.2-76.5]; P<0.001), yet consistent across age-groups (P=0.602), male/females (P=0.765), and acute/chronic-cases (P=0.157). Median (IQR) IgG titers were 110 (84-163) AU/mL, with 0.62 (0.52-0.72) avidity, supporting a long history of infection. No acute CMV infections were found. In 22.6% (n/N.=40/177) of the IgG-positive cases low-level coronary and/or systemic CMV-DNAemia (always <40 copies/mL) was detected. While no differences in peripheral CMV-DNAemia prevalence were observed nor among cases nor controls, coronary CMV-DNAemia was more frequent in acute-cases without modifiable CV risk-factors (n/N.=4/10; 40.0%), than in chronic-cases (n/N.=6/55, 10.9%; P=0.029), or acute-cases with risk-factors (n/N.=16/112, 14.3%; P=0.058)., Conclusions: CMV-IgG seroprevalence was high in patients with heart diseases. CMV-DNAemia can be found, although uncommonly, in coronary circulation during an ACS, with increased prevalence in older subjects and in absence of CV risk-factors, identifying possible areas for novel interventions.

Published
2023
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