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8. Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Author

Podlekareva, D. N., Panteleev, A. M., Grint, D., Post, F. A., Miro, J. M., Bruyand, M., Furrer, H., Obel, N., Girardi, E., Vasilenko, A., Losso, M. H., Arenas-Pinto, A., Cayla, J., Rakhmanova, A., Zeltina, I., Werlinrud, A. M., Lundgren, J. D., Mocroft, A., Kirk, O., Toibaro, J. J., Warley, E., Tamayo, N., Cristina Ortiz, M., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Skrahina, E., Skrahin, A., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., d'Arminio Monforte, A., Riekstina, V., Aldins, P., Duiculescu, D., Malashenkov, E., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes, J. L., Martinez-Lacasa, X., Falco, V., Imaz, A., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Miller, R., Chentsova, N., Podlekareva, D., Kjaer, J., and Duiculesku, D.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Multivariate analysis, Tuberculosis, Anti-HIV Agents, Antitubercular Agents, Argentina, HIV Infections, Rate ratio, Cohort Studies, symbols.namesake, Cause of Death, Coinfection, Europe, Female, Humans, Multivariate Analysis, Internal medicine, medicine, Poisson regression, Cause of death, business.industry, Mortality rate, medicine.disease, 3. Good health, Surgery, Cohort, symbols, business, Cohort study
Abstract

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (3 months, 3-12 months or12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died3 months, 3-12 months or12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Published
2014

9. Development of a post-exposure paediatric anti HIV-AIDS vaccine based on the combined synthetic/recombinant HIV peptides and BCG for boosting innate and acquired immunity. North-South transfer in Biotechnology of Tuberculosis and AIDS. University of Rome 'Tor Vergata'. UNESCO Interdisciplinary Chair in Biotechnology. Vittorio Colizzi, Luc Montagnier, 2004

Author

AMICOSANTE M, ANDREONI M, ANSELMI A, CASTELLI G, CIARAMELLA A, COLIZZI V, D'ARRIGO R, ERCOLI L, FRAZIANO M, GARG SK, MARCHIONE P, MATTEI M, PALMIERI G, PERNO F, SALTINI C, SANTUCCI M, SUMERSKA T, ROSSI P, VENDETTI S, CAPPELLI G, CAVONE A, GRASSI M, MARIANI F, MIGNONE M, PERRETTA G, CASETTI R, HOREJSH D, MARTINI F, MONTESANO C, GIOIA C, POCCIA F, PUCILLO L, SACCHI A, DI SANO C, CAIRO C, GALLO R, REDFIELD R, PAUZA D, CHENAL H, MONTAGNIER L, OLIVIER R, TONI T, MAULE L, SIMPORE J., DI GIORGIO, Giuseppa, MARTINO, Andrea, BONANNO, Cesira, DIELI, Francesco, SALERNO, Alfredo, COLIZZI V., MONTAGNIER L., AMICOSANTE M, ANDREONI M, ANSELMI A, CASTELLI G, CIARAMELLA A, COLIZZI V, D'ARRIGO R, DI GIORGIO G, ERCOLI L, FRAZIANO M, GARG SK, MARCHIONE P, MATTEI M, PALMIERI G, PERNO F, SALTINI C, SANTUCCI M, SUMERSKA T, ROSSI P, VENDETTI S, CAPPELLI G, CAVONE A, GRASSI M, MARIANI F, MIGNONE M, PERRETTA G, CASETTI R, HOREJSH D, MARTINO A, MARTINI F, MONTESANO C, GIOIA C, POCCIA F, PUCILLO L, SACCHI A, BONANNO CT, DIELI F, DI SANO C, SALERNO A, CAIRO C, GALLO R, REDFIELD R, PAUZA D, CHENAL H, MONTAGNIER L, OLIVIER R, TONI T, MAULE L, and SIMPORE J

Published
2004

11. Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients

Author

Podlekareva, D. N., Grint, D., Post, F. A., Mocroft, A., Panteleev, A. M., Miller, R. F., Miro, J. M., Bruyand, M., Furrer, H., Riekstina, V., Girardi, E., Losso, M. H., Cayla, J. A., Malashenkov, E. A., Obel, N., Skrahina, A. M., Lundgren, J. D., Kirk, O., Chentsova, N., Duiculesku, D., Toibaro, J. J., Warley, E., Tamayo, N., Ortiz, M. C., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Vasilenko, A., Skrahina, E., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., Aldins, P., Zeltina, I., Duiculescu, D., Rakhmanova, A., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes Mutua de Terrassa, J. L., Martinez-Lacasa, X., Imaz, V. F., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Arenas-Pinto, A., Kjaer, J., and Ellefson, M.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Tuberculosis, TB-HIV co-infection, Health care index score, Outcome of TB-HIV patients, TB-HIV health care utilisation, AIDS-Related Opportunistic Infections, Cause of Death, Coinfection, Delivery of Health Care, Female, Follow-Up Studies, Global Health, HIV Seropositivity, Humans, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, Health care, medicine, 030212 general & internal medicine, Cause of death, business.industry, Proportional hazards model, Retrospective cohort study, medicine.disease, 3. Good health, Surgery, Regimen, Infectious Diseases, Risk assessment, business
Abstract

OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0–5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1–3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5–1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31–48) among patients with an HCI score of 0, to 9% (95%CI 6–13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64–0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.

Published
2013

13. ISS-NIA ITALIAN COHORT: NEW ANTI-HIV INHIBITORS IN PATIENTS EXPERIENCED TO IP, NRTI, NNRTI

Author

Bucciardini, R., Floridia, M., Weimer, Le, Fragola, V., Massella, M., Baroncelli, S., Pirillo, Mf, Galluzzo, Cm, Donnini, S., Mirra, M., Di Gregorio, M., Lucattini, S., Fucili, L., Baldelli, F., Francisci, D., Martinelli, L., Bastianelli, S., Pastore, G., Ladisa, N., Volpe, A., Vullo, V., D Ettore, G., Ceccarelli, G., Andreoni, M., Sarmati, L., Delle Rose, D., Montano, M., Tozzi, V., Libertone, R., Pucillo, L., Narciso, P., Bellagamba, R., Tommasi, C., Petrosillo, N., Cicalini, S., Sighinolfi, L., Daniela Segala, Armignacco, O., Preziosi, R., Ferrari, C., Antoni, Ad, Cavalli, A., Parruti, G., Sozio, F., Cosentino, L., Dionisio, D., Vivarelli, A., Manconi, Pe, Ortu, F., Di Martino, Ml, Chiodo, F., Biagelti, C., Borderi, M., Boni, P., Del Gobbo, R., Paggi, Am, Silvestri, C., Scalise, G., Giacometti, A., Cirioni, O., Mura, Ms, Mannazzu, M., Coinu, G., Bellissima, P., Bonfante, S., Neri, D., Guaraldi, G., and Beghetto, B.

Subjects
antiretroviral therapy, HIV, COHORT STUDY, NO
Published
2009

15. Mortality from HIV and TB coinfections is higher in Eastern Europe than in Western Europe and Argentina

Author

Podlekareva, Dn, Mocroft, A, Post, Fa, Riekstina, V, Miro, Jm, Furrer, H, Bruyand, M, Panteleev, Am, Rakhmanova, Ag, Girardi, E, Losso, Mh, Toibaro, Jj, Caylá, J, Miller, Rf, Obel, N, Skrahina, A, Chentsova, N, Lundgren, Jd, Kirk, O, Collaborators: Losso MH, HIV/TB Study Writing G. r. o. u. p., Warley, E, Tamayo, N, Cristina Ortiz, M, Santojanni, F, Scapelatto, P, Bottaro, E, Murano, F, Miachans, M, Contarelli, J, Massera, L, Corral, J, Hualde, M, Miglioranza, C, Corti, M, Metta, H, Casiró, A, Cuini, R, Laplume, H, David, D, Marson, C, Lupo, S, Trape, L, Garcia Messina, O, Gear, O, Ramos Mejía JM, Bruguera, Jm, Karpov, I, Vasilenko, A, Skrahina, E, Skrahin, A, Zhavoronok, S, Mitsura, V, Ruzanov, D, Bondarenko, V, Suetnov, O, Paduto, D, Gerstoft, J, Kronborg, G, Pedersen, C, Larsen, Cs, Pedersen, G, Laursen, Al, Nielsen, L, Jensen, J, Dabis, F, Chêne, G, Lawson Ayayi, S, Thiébaut, R, Winnock, M, Bernard, N, Dupon, M, Lacoste, D, Malvy, D, Mercié, P, Morlat, P, Neau, D, Pellegrin, Jl, Ragnaud, Jm, Moreau, Jf, Blanco, P, Fleury, H, Lafon, Me, Masquelier, B, Pellegrin, I, Blaizeau, Mj, Decoin, M, Delveaux, S, Dutoit, D, Geffard, S, Hannapier, C, Houinou, L, Labarrère, S, Lavignolle Aurillac, V, Palmer, G, Touchard, D, Bonarek, M, Bonnet, F, Lacombe, K, Gellie, P, Paccalin, F, Pertusa, Mc, Dutronc, H, Dauchy, F, Lafarie, S, Longy Boursier, M, Pistonne, T, Receveur, Mc, Thibaut, P, Cazorla, C, Chambon, D, De La Taille, C, Galpérine, T, Ochoa, A, Viallard, Jf, Caubet, O, Nouts, C, Couzigou, P, Castera, L, Loste, P, Caunègre, L, Bonnal, F, Farbos, S, Gemain, Mc, Ceccaldi, J, Tchamgoue, S, Witte, Sd, Carvalho, Ac, Basché, R, Hamad, Ie, Ricci, Ba, Maggiolo, F, Ravasio, V, Mussini, C, Prati, F, Castelletti, S, Spallanzani, L, Antinori, A, Antonucci, G, Bibbolino, C, Bove, G, Busi Rizzi, E, Cicalini, S, Conte, A, Cuzzi, G, De Mori, P, Festa, A, Goletti, D, Grisetti, S, Gualano, G, Lauria, Fn, Maddaluno, R, Migliorisi Ramazzini, P, Narciso, P, Parracino, L, Palmieri, F, Petrosillo, N, Pucillo, L, Puro, V, Vanacore, P, Urso, R, Moroni, M, Carosi, Giampiero, Cauda, R, Chiodo, F, d'Arminio Monforte, A, Di Perri, G, Galli, M, Iardino, R, Ippolito, G, Lazzarin, A, Mazzotta, F, Panebianco, R, Pastore, G, Perno, Cf, Ammassari, A, Arici, C, Balotta, C, Bonfanti, P, Capobianchi, Mr, Castagna, A, Ceccherini Silberstein, F, Cozzi Lepri, A, De Luca, A, Gervasoni, C, Lo Caputo, S, Murri, R, Puoti, Massimo, Torti, Carlo, Fanti, I, Formenti, T, Prosperi, M, Montroni, M, Giacoemtti, A, Costantini, A, Riva, A, Tirelli, U, Martellotta, F, Ladisa, N, Suter, F, Verucchi, G, Fiorini, C, Carosi, G, Cristini, G, Torti, C, Minardi, C, Bertelli, D, Quirino, T, Abeli, C, Manconi, Pe, Piano, P, Pizzigallo, E, Dalessandro, M, Carnevale, G, Lorenzotti, S, Ghinelli, F, Sighinolfi, L, Leoncini, F, Pozzi, M, Pagano, G, Cassola, G, Viscoli, G, Alessandrini, A, Piscopo, R, Soscia, F, Tacconi, L, Orani, A, Rossotto, R, Tommasi, D, Congedo, P, Chiodera, A, Castelli, P, Rizzardini, G, Schlacht, I, Ridolfo, Al, Foschi, A, Salpietro, S, Merli, S, Melzi, S, Moioli, Mc, Cicconi, P, Esposito, R, Gori, A, Borrello, A, Abrescia, N, Chirianni, A, Izzo, Cm, De Marco, M, Viglietti, R, Manzillo, E, Ferrari, C, Pizzaferri, P, Baldelli, F, Camanni, G, Magnani, G, Ursitti, Ma, Arlotti, M, Ortolani, P, Andreoni, M, Tozzi, V, Vullo, V, Zaccarelli, M, Acinapura, R, De Longis, P, Trotta, Mp, Lichtner, M, Carletti, F, Mura, Ms, Madeddu, G, Caramello, P, Orofino, Gc, Raise, E, Ebo, F, Pellizzer, G, Buonfrate, D, Aldins, P, Duiculescu, D, Rakhmanova, A, Malashenkov, E, Kozlov, A, Panteleev, A, Buzunova, S, García Goez JF, Moreno Camacho, A, Martínez, Ja, González, J, García Alcaide, F, de Lazzari, E, Gatell, Jm, Sanchez, P, Lopez Colomes JL, Martínez Lacasa, X, Falcó, V, Imaz, A, Ocaña, I, Vidal, R, Sambeat, Ma, Caylà, J, Moreno Martínez, A, Orcau, A, Weber, R, Battegay, M, Hirschel, B, Cavassini, M, Bernasconi, E, Schmid, P, Rickenbach, M, Post, F, Campbell, L, Miller, R, Arenas Pinto, A, Podlekareva, D, Kjaer, J, Ellefson, M, and Toibaro, J. J.

Subjects
HIV/TB coinfection, Eastern Europe, Western Europe, Argentina
Published
2009

17. CD1d expression by hepatocytes is a main restriction element for intrahepatic T-cell recognition

Author

Agrati, C., Martini, F., Nisii, C., Oliva, A., D Offizi, G., Narciso, P., Nardacci, R., Piacentini, M., Francesco Dieli, Pucillo, L. P., and Poccia, F.

Subjects
Adult, Male, Antigen Presentation, T-Lymphocytes, Genes, MHC Class I, Cell Communication, Hepacivirus, Middle Aged, Flow Cytometry, Hepatitis C, Immunohistochemistry, CD56 Antigen, Hepatitis D, Antigens, CD1, Killer Cells, Natural, Liver, Hepatocytes, Leukocytes, Mononuclear, Humans, Female, Lymphocytes, Antigens, CD1d, Glycolipids, Aged
Abstract

The liver has specific mechanisms to protect itself from infectious agents and to avoid autoimmunity, indicating an important role of the hepatic tissues in antigen presentation and tolerance induction. Since intrahepatic lymphocytes may contribute to the innate immunity and to the liver pathology, it is of interest to analyze the expression of antigen presenting molecules and of the related T cell recognition in liver, and how these change in relation to different diseases. We analyzed the expression of MHC class I, and of CD1-a, -b, -c, and -d proteins on liver tissues from patients with different hepatic diseases. Moreover, in the same patients we studied the intrahepatic and peripheral NKT cell recognition of alpha-galactosyl ceramide antigen in the context of CD1d. Unlike in other tissues, classical MHC class I molecules were poorly expressed in the hepatic compartment, suggesting that inflamed hepatocytes may trigger weak MHC-restricted T cell responses. Nevertheless, we observed a prevalent expression of HLA class I-like CD1d isoform on the hepatocyte surface, indicating that CD1d is the main restriction element in the liver. In patients with viral hepatitis, the intrahepatic CD1d expression parallels the recruitment of CD56+Valpha24Vbeta11+ NKT cells in the liver which recognize CD1d presenting glycolipids such as alpha-galactosyl ceramide, suggesting that the intrahepatic T cell immunity may focus on glycolipid antigens.

Published
2005

19. Antiviral activity and anergy of gammadeltaT lymphocytes in cord blood and immuno-compromised host

Author

Montesano, C, Gioia, C, Martini, F, Agrati, C, Cairo, C, Pucillo, L, Colizzi, V, and Poccia, F

Subjects
Adult, Settore MED/04 - Patologia Generale, gamma-delta, C-Type, Tumor Necrosis Factor-alpha, T-Lymphocytes, Infant, HIV Infections, T-Cell, Fetal Blood, Newborn, CD, Interferon-gamma, T-Lymphocyte, HLA Antigens, Antigen, Differentiation, Lectins, Receptors, Immune Tolerance, Humans, Interleukin-2, Receptors, Antigen, T-Cell, gamma-delta, Antigens, Differentiation, T-Lymphocyte, Antigens, CD, Receptors, Interleukin-2, Infant, Newborn, Lectins, C-Type, Antigens
Published
2001

22. Different Cytokine Production and Effector/Memory Dynamics of αβ+ or γδ+ T-Cell Subsets in the Peripheral Blood of Patients with Active Pulmonary Tuberculosis

Author

Gioia, C., primary, Agrati, C., additional, Goletti, D., additional, Vincenti, D., additional, Carrara, S., additional, Amicosante, M., additional, Casarinp, M., additional, Giosue, S., additional, Puglisi, G., additional, Rossi, A., additional, Colizzi, V., additional, Pucillo, L. P., additional, and Poccia, F., additional

Published
2003
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26. The Loss of CMV-Specific CD27− T-Cell Effectors in a Patient with Recurrences of CMV Retinitis Is Independent of HIV-1 Viremia.

Author

D'Offizi, G., Ciapparoni, V., Gioia, C., Goletti, D., Agrati, C., Pucillo, L. P., Narciso, P., and Poccia, F.

Subjects
LETTERS to the editor, HIV infections, CYTOMEGALOVIRUS diseases, ANTIRETROVIRAL agents
Abstract

Presents a letter to the editor about a 42-year-old man with HIV disease who developed multiple recurrences of cytomegalovirus retinitis, despite receiving highly active antiretroviral therapy.

Published
2002
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27. Formalin-treated bacteria as selective B cell mitogens: Results in primary and acquired immunodeficiencies

Author

Sirianni, M. C., Pucillo, L. P., MASSIMO FIORILLI, Aiuti, F., Banck, G., and Forsgren, A.

Subjects
Adult, Male, B-Lymphocytes, Adolescent, Bacteria, Immunologic Deficiency Syndromes, Infant, Lymphocyte Activation, Leukemia, Lymphoid, Child, Preschool, Formaldehyde, Humans, Female, Mitogens, Child, Cell Division, Research Article
Abstract

The mitogenic activity of the formalin-treated bacterial strains Branhamella catarrhalis, Haemophilus influenzae and the Cowan I strain of Staphylococcus aureus was assessed in peripheral blood lymphocytes (PBL) from patients with primary immunodeficiencies, acute lymphocytic leukaemia (ALL), chronic lymphocytic leukemia (CLL) and in umbilical cord blood lymphocytes. The bacteria selectively stimulated B cells, as demonstrated by the finding of a normal de novo DNA synthesis in children with a T cell defect and of an absent response in X-linked agammaglobulinaemia and severe combined immunodeficiency. A decreased mitogenic activity was exerted on PBL from four out of seven adults with common variable hypogammaglobulinemia (CVH). In B-CLL the mitogenic activity was normal while in T-ALL it was decreased. Umbilical cord blood lymphocytes responded better than PBL from adults. The selective stimulative ability of the bacteria for B lymphocytes is expressed when PBL are cultured together with the formalin-treated bacteria for 48 to 72 hr.

30. Three-years follow up of raltegravir and/or maraviroc-based regimens in patients experienced to PI, NRTI, NNRTI. Update from the ISS-NIA cohort

Author

Weimer, L. E., Floridia, M., Bucciardini, R., Baroncelli, S., Galluzzo, C. M., Pirillo, M. F., Fragola, V., Donnini, S., Mirra, M., Di Gregori, M., Lucattini, S., Fucili, L., Baldelli, F., Francisci, D., Schiarol, E., Bastianelli, S., Angarano, G., Ladisa, N., Volpe, A., Vullo, V., D’ettore, G., Ceccarelli, G., Andreoni, M., Sarmati, L., Delle Rose, D., Tozzi, V., Libertone, R., Pucillo, L., Bellagamba, R., Petrosillo, N., Cicalini, S., Sighinolfi, L., Daniela Segala, Armignacco, O., Preziosi, R., Ferrari, C., Degli Antoni, A., Cavalli, A., Parruti, G., Sozio, F., Cosentino, L., Vivarelli, A., Manconi, P. E., Ortu, F., Di Marti, L., Viale, P., Verucchi, G., Tedeschi, S., Tavio, M., Del Gobbo, R., Mataloni Paggi, A., Giacometti, A., Cirioni, O., Marchionni, E., Barchiesi, F., Brescini, L., Morone, P., Mazzocato, S., Mura, M. S., Mannazzu, M., Guaraldi, G., Beghetto, B., and Nardini, G.

Subjects
NO

34. Resistance to recombinant alpha interferon therapy in idiopathic mixed cryoglobulinemia: Reinduction of remission by natural alpha interferon both in antibody-positive and -negative patients

Author

MILVIA CASATO, Antonelli, G., Maggi, F., Pucillo, L. P., Di Lullo, L., Leoni, M., Currenti, M., Dianzani, F., and Bonomo, L.

Subjects
Antibodies, Cryoglobulinemia, Drug Resistance, Humans, Interferon-alpha, Neutralization Tests, Recombinant Proteins, Recurrence, Remission Induction, Interferon alpha-2
Abstract

A subset of patients treated with recombinant interferon alpha-2a (rIFN-alpha 2a) for idiopathic mixed cryoglobulinemia (IMC) developed clinical resistance to therapy after a sustained response. Neutralizing antibodies to rIFN-alpha 2a were found in the sera of three out of four such patients, and in none of the patients who remained responsive to treatment. rIFN-alpha 2a neutralizing antibodies appeared in serum samples of the former three patients 1, 5 and 6 months before evidence for clinical resistance, respectively. Antibody titres to rIFN-alpha 2a were consistently higher than those to natural interferon (nIFN). In the fourth patient with clinical resistance, neutralizing antibodies could not be detected by a very sensitive bioassay in any of several serum samples taken before and after relapse. All the four patients could be reinduced into remission by the administration of nIFN-alpha. These data indicate that mechanisms other than the production of neutralizing antibodies can mediate acquired resistance to IFN therapy. Furthermore, both antibody-related and -unrelated resistance can be overcome by switching to different species of IFN-alpha.

36. Lymphocyte distribution and intrahepatic compartmentalization during HCV infection: a main role for MHC-unrestricted T cells

Author

Chiara Agrati, Nisii, C., Oliva, A., D Offizi, G., Montesano, C., Pucillo, L. P., and Poccia, F.

Subjects
Settore MED/04 - Patologia Generale, gamma-delta, T-Cell, Hepatitis C, Lymphocyte Subsets, Liver, T-Lymphocyte Subsets, Antigen, Receptors, Natural, Cytokines, Animals, Killer Cells, Humans, Inflammation Mediators, Receptors, Antigen, T-Cell, gamma-delta, Killer Cells, Natural

37. Marked increase in etravirine and saquinavir plasma concentrations during atovaquone/proguanil prophylaxis

Author

Ivanovic Jelena, Gallo Anna L, D'Avolio Antonio, Tempestilli Massimo, Bellagamba Rita, Tommasi Chiara, Nicastri Emanuele, Pucillo Leopoldo P, and Narciso Pasquale

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract The case of a 32-year-old Caucasian female with multi-drug resistant HIV-1 subtype B infection treated with a salvage regimen including maraviroc, raltegravir, etravirine and unboosted saquinavir who started atovaquone/proguanil prophylaxis, is reported. The potential interactions between atovaquone/proguanil and these anti-retroviral drugs are investigated. Pharmacokinetic analyses documented a marked increase in etravirine and saquinavir plasma concentrations (+55% and +274%, respectively), but not in raltegravir and maraviroc plasma concentrations. The evidence that atovaquone/proguanil significantly interacts with etravirine and saquinavir, but not with raltegravir and maraviroc, suggests that the mechanism of interaction is related to cytochrome P450.

Published
2011
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38. Cryoglobulinaemia and hepatitis C virus.

Author

Casato, M, Taliani, G, Pucillo, L P, Goffredo, F, Laganà, B, and Bonomo, L

Subjects
*VASCULAR diseases, *CHRONIC diseases, *DIAGNOSTIC reagents & test kits, *HEMOSTASIS, *HEPATITIS, *HEPATITIS viruses, *VIRAL antibodies, *DISEASE complications
Published
1991
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39. Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload

Author

Leopoldo Paolo Pucillo, Andrea Baiocchini, Carmine Mancone, Franca Del Nonno, Marco Tripodi, Vera van Noort, Tonino Alonzi, Claudia Montaldo, Nicolina Rotiroti, Giuseppe Ippolito, Laura Amicone, Alice Conigliaro, Angela Maria Cozzolino, Cecilia Battistelli, Simone Mattei, Montaldo, C., Mattei, S., Baiocchini, A., Rotiroti, N., Nonno, F., Pucillo, L., Cozzolino, A., Battistelli, C., Amicone, L., Ippolito, G., van Noort, V., Conigliaro, A., Alonzi, T., Tripodi, M., Mancone, C., Department of Cellular Biotechnologies and Haematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), L. Spallanzani, National Institute for Infectious Diseases (IRCCS), European Molecular Biology Laboratory [Heidelberg] (EMBL), and This work was supported by grants from MIUR Ministero dell’Universit `a e Ricerca Scientifica (FIRB 2012, codice progetto RBFR12NSCF), Associazione Italiana per la Ricerca sul Cancro (AIRC) andMinistero della Salute (Ricerca Finalizzata 40H27, Ricerca Corrente).

Subjects
Liver Cirrhosis, Proteomics, hepatitis C virus, Male, MESH: Isotope Labeling, HSC, medicine.disease_cause, Biochemistry, 0302 clinical medicine, Fibrosis, MESH: Up-Regulation, Membrane Protein, hepatic stellate cell, liver fibrosis, hepatic iron overload, 0303 health sciences, biology, MESH: Proteomics, Medicine (all), hepatocellular carcinoma, Biomedicine, hepatitis c infection, vitronectin, Hepatitis C, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Up-Regulation, 3. Good health, cell culture-derived HCV, Isotope Labeling, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Hepatic iron overload, Hepatitis C infection, Liver fibrosis, Vitronectin, Biomarkers, Cell Line, Humans, Iron Overload, Membrane Proteins, Molecular Biology, HCV, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Biomarker (medicine), MESH: Membrane Proteins, MESH: Liver Cirrhosis, Human, Liver Cirrhosi, Hepatitis C virus, MESH: Iron Overload, 03 medical and health sciences, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Hepatitis C, MESH: Humans, MESH: Biological Markers, Liver fibrosi, Proteomic, Biomarker, medicine.disease, MESH: Vitronectin, MESH: Male, digestive system diseases, MESH: Cell Line, Biomedicine / Abbreviations: HCC, HCVcc, Immunology, Cancer research, Hepatic stellate cell, biology.protein, Steatosis
Abstract

Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighted the hepatocytic vitronectin expression as the most promising specific biomarker for iron-associated fibrogenesis in HCV infections. Next, the robustness of our in vitro findings was challenged in human liver biopsies by immunohistochemistry and yielded two major results: (i) hepatocytic vitronectin expression is associated to liver fibrogenesis in HCV-infected patients with iron overload; (ii) hepatic vitronectin expression was found to discriminate also the transition between mild to moderate fibrosis in HCV-infected patients without iron overload. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Published
2014
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40. RESEARCH NOTE Evaluation of the BDProbeTec strand displacement amplification assay in comparison with the AMTD II direct test for rapid diagnosis of tuberculosis.

Author

Visca, P., De Mori, P., Festa, A., Montrone, M. L., Amicosante, M., and Pucillo, L. P.

Subjects
*MYCOBACTERIUM tuberculosis, *TUBERCULOSIS, *ZIEHL-Neelsen stain, *MYCOBACTERIA identification, *MICROBIOLOGY, *BIOLOGICAL assay
Abstract

The BDProbeTec MTB assay for direct detection of Mycobacterium tuberculosis was evaluated in comparison with the AMTD-II assay on 94 samples from different patients with clinical suspicion of tuberculosis. Using a combination of culture on Lowenstein–Jensen medium (with or without preculture in BACTEC 9000) and clinical diagnosis as the standard, BDProbeTec MTB showed high sensitivity and specificity (96.1% and 100%, respectively), similar to AMTD-II (96.1% and 97.1%, respectively), with significantly higher sensitivity than the Ziehl–Neelsen stain for acid-fast bacilli (73%, p < 0.05). [ABSTRACT FROM AUTHOR]

Published
2004
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41. Dendritic cells derived from BCG-infected precursors induce Th2-like immune response

Author

Nunzia Sanarico, Leopoldo Paolo Pucillo, Vittorio Colizzi, Antonio Ciaramella, Carlo Ramoni, Angelo Martino, Silvia Vendetti, Alessandra Sacchi, Francesca Spadaro, Martino, A., Sacchi, A., Sanarico, N., Spadaro, F., Ramoni, C., Ciaramella, A., Pucillo, L. P., Colizzi, V., and Vendetti, S.

Subjects
Lipopolysaccharides, Immunology, CD1a, Biology, complex mixtures, Peripheral blood mononuclear cell, Monocytes, Proinflammatory cytokine, Th2 Cells, Immune system, Polarization, medicine, Humans, Immunology and Allergy, Cytokine, Monocyte, Mycobacteria, Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin, hemic and immune systems, Cell Differentiation, Dendritic Cells, Cell Biology, Fetal Blood, Mycobacterium bovis, Coculture Techniques, medicine.anatomical_structure, Differentiation, BCG Vaccine, Cytokines, Tumor necrosis factor alpha, Tuberculosis vaccines, BCG vaccine
Abstract

Human monocytes can differentiate into dendritic cells (DCs) according to the nature of environmental signals. We tested here whether the infection with the live tuberculosis vaccine bacillus Calmette-Guerin (BCG), which is known to be limited in preventing pulmonary tuberculosis, modulates monocyte and DC differentiation. We found that monocytes infected with BCG differentiate into CD1a– DCs (BCG-DCs) in the presence of granulocyte macrophage-colony stimulating factor and interleukin (IL)-4 and acquired a mature phenotype in the absence of maturation stimuli. In addition, BCG-DCs produced proinflammatory cytokines (tumor necrosis factor α, IL-1β, IL-6) and IL-10 but not IL-12. BCG-DCs were able to stimulate allogeneic T lymphocytes to a similar degree as DCs generated in the absence of infection. However, BCG-DCs induced IL-4 production when cocultured with human cord-blood mononuclear cells. The induction of IL-4 production by DCs generated by BCG-infected monocytes could explain the failure of the BCG vaccine to prevent pulmonary tuberculosis.

Published
2004
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42. Non-pathogenic Mycobacterium smegmatis induces the differentiation of human monocytes directly into fully mature dendritic cells

Author

Alessandra Sacchi, Elisabetta Volpe, Leopoldo Paolo Pucillo, Angelo Martino, Silvia Vendetti, Chiara Agrati, Vittorio Colizzi, Rafaella De Santis, Martino, A., Sacchi, A., Volpe, E., Agrati, C., De Santis, R., Pucillo, L. P., Colizzi, V., and Vendetti, S.

Subjects
Adult, Adolescent, T-Lymphocytes, Mycobacterium smegmatis, Immunology, Antigen presentation, Cell Communication, CD1a, Monocytes, Microbiology, Th2 Cells, Immune system, Humans, Immunology and Allergy, Monocyte differentiation, Cells, Cultured, biology, Follicular dendritic cells, Tumor Necrosis Factor-alpha, CLEC7A, Cell Differentiation, Dendritic Cells, Th1 Cells, Hematopoietic Stem Cells, Acquired immune system, biology.organism_classification, Interleukin-12, Interleukin-10, Interleukin 12, M. smegmati, Dendritic cell
Abstract

Mycobacterium smegmatis infects human monocytes that can be precursors of dendritic cells. We tested whether the interaction of M. smegmatis with monocytes modulated their differentiation into dendritic cells. We found that M. smegmatis-infected monocytes differentiated into CD1a-CCR7 + dendritic cells in the presence of GM-CSF and IL-4 and acquired a mature phenotype since they expressed CD83 molecules in the absence of maturation stimuli. Dendritic cells derived from M. smegmatis-infected monocytes stimulated with bacterial products, produced IL-10 and still retained the capacity to produce IL-12. Consequently, they polarized naïve T lymphocytes towards a mixed Th1/Th2 immune response inducing both IFN-γ and IL-4 production. These findings suggest that the exposure to environmental mycobacteria could modulate the differentiation of dendritic cells making them able to migrate into secondary lymphoid organs and modulate the adaptive immune response. This could explain one of the mechanisms by which environmental mycobacteria can influence the immune response to pathogenic species. © 2005 Springer Science+Business Media, Inc.

Published
2005

43. Interferon for hepatitis C virus-negative type II mixed cryoglobulinemia.

Author

Casato, Milvia, Lagana, Bruno, Pucillo, Leopoldo P., Quinti, Isabella, Casato, M, Lagana, B, Pucillo, L P, and Quinti, I

Subjects
*LETTERS to the editor, *HEPATITIS C virus, *HEMOSTASIS, *THERAPEUTIC use of proteins, *HEPATITIS C, *RECOMBINANT proteins, *THERAPEUTICS, TREATMENT of vascular diseases
Abstract

A letter to the editor about the Hepatitis C virus is presented.

Published
1998
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44. 25-Hydroxyvitamin D Plasma Levels in Natural Populations of Pigmented and Partially Pigmented Land Iguanas from Galápagos ( Conolophus spp.).

Author

Di Giacomo C, Pucillo L, Sevilla C, Fucci G, Massoud R, Bernardini S, Fraziano M, and Gentile G

Subjects
Animals, Ecuador, Vitamin D analogs & derivatives, Iguanas, Lizards
Abstract

We report the first data on 25-hydroxyvitamin D plasma levels in natural populations of three species of land iguana endemic to the Galápagos Islands ( Conolophus marthae , C. subcristatus , and C. pallidus ). The pigment is present throughout the whole body in the skin of C. subcristatus and C. pallidus . On the contrary, pigment is not present in the skin of an extended part of the body in C. marthae . The only existing population of C. marthae is syntopic with a population of C. subcristatus , and the two species are closely related. These circumstances would suggest that, under the assumption that the species show a similar basking behavior and in the absence of compensatory mechanisms, lighter pigmentation should favor higher vitamin D levels. Thus, C. marthae , compared with C. subcristatus in Wolf Volcano, could show higher levels of 25(OH)D plasma levels, or equal, if compensatory mechanisms exist. The three species showed levels in the range of average values for healthy iguanas. However, contrary to the expectation, C. marthae consistently exhibited the lowest 25(OH)D plasma levels. We discuss possible factors affecting vitamin concentration and hypothesize that C. marthae may use the habitat to limit exposure to the high UVB irradiation at Wolf Volcano., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Cristina Di Giacomo et al.)

Published
2022
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45. Low-density lipoprotein and ritonavir: an interaction between antiretrovirals and lipids mediated by P-glycoprotein.

Author

Tempestilli M, Elisei F, Cimini E, D'Avolio A, Grassi G, Nicastri E, Narciso P, Martini F, Alonzi T, and Paolo Pucillo L

Subjects
Cell Line, Chromatography, High Pressure Liquid, Cytosol chemistry, Flow Cytometry, Gene Expression Profiling, Humans, Monocytes, Protein Binding, Real-Time Polymerase Chain Reaction, Spectrophotometry, Ultraviolet, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Anti-HIV Agents metabolism, Anti-HIV Agents pharmacokinetics, Lipoproteins, LDL metabolism, Ritonavir metabolism, Ritonavir pharmacokinetics
Abstract

Background: Antiretroviral therapy has considerably reduced HIV disease progression, but complete eradication of HIV cannot actually be achieved. Moreover, prolonged use of protease inhibitors (PIs) causes profound changes in lipid metabolism with an increased risk of cardiovascular diseases. P-glycoprotein (P-gp) is expressed on many cell types, playing an important role in the efflux of drugs including PIs, limiting their intracellular concentration. Furthermore, several studies showed that P-gp is involved in lipid homeostasis and its activity is regulated by cholesterol., Methods: THP-1 monocytes were used to study: (i) the influence of low-density lipoprotein (LDL) on P-gp expression and function, assessed by flow cytometry and quantitative real-time PCR analysis and measuring ritonavir and rhodamine-123 dye efflux, respectively; and (ii) the influence of ritonavir on cholesterol mobilization. The intracellular levels of ritonavir or cholesterol were measured by HPLC-UV and filipin staining, respectively., Results: In THP-1 cells, LDL was able to yield an increase in both P-gp expression and activity. THP-1 cells treated with LDL showed a decrease in the intracellular ritonavir concentration in a dose-dependent manner. Notably, ritonavir induced reduced cholesterol mobilization in THP-1 cells, probably due to its inhibitory action on P-gp activity., Conclusions: Our data indicate a potential interplay between LDL and ritonavir mediated by P-gp. This interaction could influence both therapy effectiveness and cellular lipid metabolism, with important implications in the management of HIV patients treated with boosted PIs., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Published
2014
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46. Cystic echinococcosis in a single tertiary care center in Rome, Italy.

Author

Petrone L, Cuzzi G, Colace L, Ettorre GM, Busi-Rizzi E, Schininà V, Pucillo L, Angeletti C, Pane S, Di Caro A, Bordi E, Girardi E, Pozio E, Corpolongo A, Teggi A, Brunetti E, and Goletti D

Subjects
Adult, Animals, Cysts pathology, Echinococcosis epidemiology, Echinococcus pathogenicity, Humans, Italy, Liver parasitology, Male, Middle Aged, Echinococcosis therapy, Liver pathology, Tertiary Care Centers
Abstract

Background: Cystic echinococcosis (CE) is a chronic, clinically complex, and neglected disease. Its prevalence in Italy, a country of medium to high endemicity, remains poorly defined, as notification has long ceased to be mandatory., Methods: We set up a retrospective cohort study involving all CE patients followed at our institute between January 2005 and December 2012. Demographical and clinical features were recorded and analyzed., Results: CE was found in 28 patients (64.3%), mostly Italians from the central regions (50%), followed by subjects from the islands (33.3%) and Southern Italy (16.7%). Their median age was 45 years (IQR: 38.5-66.5), with Eastern Europeans being significantly younger (28 years, IQR: 19-39) than other patients (P ≤ 0.0001). A total of 149 cysts, mostly with hepatic localization (96%), were described. Based on the WHO classification, the cysts were mainly small (80.5%) and active (CE1 (73.8%); CE2 (7.4%)). Active cysts were more common in Eastern Europeans (85.7%) than Italians (66.7%)., Conclusion: Our data confirm CE occurrence in Italy. We emphasize the importance to have a national CE registry, opportunely recently introduced. This is essential to assess CE prevalence in this country, implement appropriate control measures, and improve patient management.

Published
2013
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47. Effect of raltegravir on the total and unintegrated proviral HIV DNA during raltegravir-based HAART.

Author

Nicastri E, Tommasi C, Abbate I, Bonora S, Tempestilli M, Bellagamba R, Viscione M, Rozera G, Gallo AL, Ivanovic J, Amendola A, Pucillo L, Di Perri G, Capobianchi MR, and Narciso P

Subjects
Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Female, HIV Infections virology, HIV-1 genetics, Humans, Leukocytes, Mononuclear virology, Male, Middle Aged, Proviruses genetics, Raltegravir Potassium, Viral Load, Virus Integration drug effects, Virus Integration genetics, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Proviruses drug effects, Pyrrolidinones therapeutic use
Abstract

Background: Raltegravir is the first approved antiretroviral able to prevent HIV genome integration into the host chromosomes. The aim of the study is to test if raltegravir plasma concentrations can be associated with proviral DNA decline during raltegravir-based salvage therapy., Methods: A total of 33 multidrug-resistant HIV-infected patients were enrolled in a longitudinal open-label pilot study and completed a 24-week follow-up. The CD4(+) T-cell count, plasma viral load, proviral HIV DNA and two-long-terminal repeat (2-LTR) circular forms were assessed at baseline, day 14, 30, 60, 90 and 180. The raltegravir trough concentration (C (trough)) was measured by HPLC-ultraviolet and patients were divided into two groups according to the median raltegravir C (trough)., Results: The mean±SD values of baseline HIV RNA, CD4(+) T-cell count and HIV DNA were 4.4±0.82 log copies/ml, 256±177 cells/mm(3) , and 2,668±4,721 copies/10(6) peripheral blood mononuclear cells, respectively. Despite a transient increase of total DNA at week 2, a marked proviral DNA decay (P=0.01) with an increase of the 2-LTR unintegrated/total DNA ratio (P=0.06) over time was observed. At univariate analysis, no correlation between raltegravir C(trough) and classical virological parameters was observed. Nevertheless, the decay of proviral HIV DNA was more pronounced in patients displaying C(trough)<158 ng/ml with respect to those with C(trough)>158 ng/ml (P=0.046)., Conclusions: Successful raltegravir-based therapy produces a significant decline in proviral DNA and is associated with an increase of the unintegrated/total DNA ratio. Further studies are necessary to define the possible role of pharmacokinetic raltegravir monitoring and the biological meaning of unintegrated proviral DNA., (© 2011 International Medical Press)

Published
2011
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48. Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones.

Author

Pasca MR, Degiacomi G, Ribeiro AL, Zara F, De Mori P, Heym B, Mirrione M, Brerra R, Pagani L, Pucillo L, Troupioti P, Makarov V, Cole ST, and Riccardi G

Subjects
Base Sequence, DNA Primers genetics, DNA, Bacterial genetics, Drug Resistance, Multiple, Bacterial genetics, Europe, Genes, Bacterial, Humans, In Vitro Techniques, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis enzymology, Mycobacterium tuberculosis genetics, Racemases and Epimerases genetics, Antitubercular Agents pharmacology, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Spiro Compounds pharmacology, Thiazines pharmacology, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology
Abstract

The new antitubercular drug candidate 2-[2-S-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase. To monitor the potential development of benzothiazinone (BTZ) resistance, a total of 240 sensitive and multidrug-resistant Mycobacterium tuberculosis clinical isolates from four European hospitals were surveyed for the presence of mutations in the dprE1 gene and for BTZ susceptibility. All 240 strains were susceptible, thus establishing the baseline prior to the introduction of BTZ043 in clinical trials.

Published
2010
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49. Does sphingosine 1-phosphate play a protective role in the course of pulmonary tuberculosis?

Author

Garg SK, Santucci MB, Panitti M, Pucillo L, Bocchino M, Okajima F, Bisen PS, Saltini C, and Fraziano M

Subjects
Adult, Animals, Cells, Cultured, Cricetinae, Female, Humans, Lysophospholipids pharmacology, Male, Middle Aged, Mycobacterium tuberculosis drug effects, Sphingosine metabolism, Sphingosine pharmacology, Tuberculosis, Pulmonary pathology, Lysophospholipids metabolism, Sphingosine analogs & derivatives, Tuberculosis, Pulmonary metabolism, Tuberculosis, Pulmonary microbiology
Abstract

Sphingosine 1-phosphate (S1P) has recently been reported to induce antimycobacterial activity in vitro and in a mouse model of in vivo Mycobacterium tuberculosis infection. However, its role in the course of pulmonary tuberculosis in humans is still not known. This study shows that S1P levels in airway surface fluid of tuberculosis (TB) patients are significantly less than those observed in non-TB control patients. Moreover, the in vitro stimulation of bronchoalveolar lavage cells coming from TB patients with S1P significantly reduces intracellular growth of endogenous mycobacterial isolates. These results show that, in the course of pulmonary TB, airway epithelial fluid-associated S1P may play a protective role in the containment of intracellular mycobacterial growth and that its decrease may represent a novel pathogenic mechanism through which M. tuberculosis favors its replication.

Published
2006
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50. Different cytokine production and effector/memory dynamics of alpha beta+ or gamma delta+ T-cell subsets in the peripheral blood of patients with active pulmonary tuberculosis.

Author

Gioia C, Agrati C, Goletti D, Vincenti D, Carrara S, Amicosante M, Casarini M, Giosue S, Puglisi G, Rossi A, Colizzi V, Pucillo LP, and Poccia F

Subjects
Adult, Female, Humans, Male, Middle Aged, T-Lymphocyte Subsets immunology, Tuberculosis, Pulmonary blood, Cytokines blood, Immunologic Memory, Receptors, Antigen, T-Cell, alpha-beta blood, Receptors, Antigen, T-Cell, gamma-delta blood, T-Lymphocyte Subsets metabolism, Tuberculosis, Pulmonary immunology
Abstract

Immunity to M.tuberculosis (MTB) infection consists of interactions between various T-cell subsets that control the infection and prevent further reactivation. We analysed the effector/memory T-cell dynamics and cytokines production in the peripheral blood of patients with pulmonary tuberculosis (TB). We observed that the frequency of CD4+ T-cell effectors was significantly increased during active TB, confirming a major role of this T-cell subset in TB immunity. Pre-terminally differentiated CD8+ T-lymphocytes were increased in the peripheral blood as well. In contrast, we observed a reduced number of effector mycobacteria-reactive gammadelta+ T-lymphocytes with a specific defects in reacting to mycobacterial nonpeptidic antigens, suggesting that this innate response is rapidly lost during TB infection. Nevertheless, the frequency of gammadelta+ T-cells effectors in TB patients was higher than the alphabeta+ T-cell response to peptide from MTB-ESAT-6 protein and quantitatively similar to PPD reactivity. Thus, alphabeta+ and gammadelta+ T-cell differentiation and function are differently triggered by active TB infection.

Published
2003
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