| Autor: |
J. Fanning, M. Keuth, E. Cagwin, E. Lachassinne, S. Campbell, K. Jeffries, J. Tutko, L. Vladau, Raffaele Badolato, Paolo Palma, J. Orendi, I. Colombo, A. Buckton, J. Neubert, Y. Rodriguez Lozano, V. Novelli, E. Belfrage, M. della Negra, N. Boudjoudi, R. Nickel, F. Schumacher, A. Furcas, J. Navarra, C. B. S. de Souza, B. Zöhrer, M. Neely, G. Pontrelli, D. Duiculescu, M. Clapson, K. A. Contello, G. Kudesia, R. Santos, Catherine Dollfus, Raffaella Rosso, G. Lewis, A. Sarah Walker, James Homans, Pier-Angelo Tovo, T. Chen, K. Fidler, V. Reliquet, A. Aali, J. Cottalorda, D. Michalik, Barbra Murante, Marisa Zanchetta, Jaime G. Deville, P. McNeil, Z. Shah, K. O’connor, H. Haley, M. I. Gonzalez Tomé, M. C. Cervi, Rosa Bologna, Abdel Babiker, D. Hamadache, A. Pala, Merlin L. Robb, E. Voicu, Cristina Bertulli, A. Smyth, G. Hadjou, L. Lugo, M. Burke, E. Hayes, Janice Hodge, Marco Tabone, Ram Yogev, A. Jurgrau, Lucia de Araujo Evangelista, K. Nguyen, P. Kamara, N. Le Gueyades, D. Picard, A. Dehée, J. Leleu, D. M. Ferraro, F. Damond, Iraina Fernandes, S. Bradford, K. Swaby, Laura Schneider, Albert Faye, T. Dunaway, Carlo Giaquinto, D. Otelea, C. Jennings, D. Gibb, J. Horton, G. Alexandre-Castor, D. Muir, A. Mazzei, J. Nelson, M. Snelling, M.J. Mellado Peña, S. Welch, C. Belmega, B. V.M. Negrini, L. Garrovillo, S. Walters, C. Müller, Andrew Collinson, Lynda Harper, T. Fleming, C. Concato, Polly Clayden, K. Elkins, A. Schnuriger, I. Farias, Caroline Foster, M. C. Sapia, L. Alecsandru, A. Alvarez, A. Waters, N. O’sullivan, S. Buskirk, Yacine Saidi, R. Pineiro Perez, Elaine J. Abrams, Y. C. Lian, L. Buck, H. Tchidjou, M. Gonzalez, S. Blanche, M. E. Paul, Leonard B. Weiner, K. Moshal, S. Marino, S. Wong, Angela Berzi, D. P. Pacola, A. Rodallec, C. Frillici, C. Rodriguez, Cristiana Oprea, L. Dehache, Anthony C. Gordon, Christine Rouzioux, P. Valentin, Jay A. Levy, Sharon Nachman, Andrea Kovacs, J. Batra, R. Croteau, I. L. Febo, Yvonne J. Bryson, P. Archer, Z. Benabadji, M. Stevanovic, E. Hutchison, G. Boddy, M. Ilie, K. Kabat, C. Monrose, Vania Giacomet, Marianne C. Jacobsen, Antonio Mazza, N. Patel, C. Farmer, A. Krivine, I. Fineanganofo, M. García López, C. Graisbery, CS Peckham, F. Monpoux, William Borkowsky, M. Denon, A. Doyle, T. Schmitz, Ann J. Melvin, Gareth Tudor-Williams, Osvalda Rampon, L. Marty, M. Sellier, M. Fernandez, Marc Foca, C. Hayes, C. Peiser, T. C. Matsubara, A. Finn, P. Martín Fontelos, W. A. Holz, A. Zoccano, Mike Sharland, R. Dersimonian, S. Champion, M. Kline, D. Collins, J.T. Ramos Amador, Angela Di Martino, Hermione Lyall, Christine A. Powell, Stephen A. Spector, J. Swan, S. Eloby-Childress, S. Yeadon, C. McMullen-Jackson, A. L. Chang, Diana M. Gibb, Henriette J. Scherpbier, G. Ball, Hannah Castro, Elena Spinelli, M. Jervis, G. Delommois, S. Scott, I. Garcia Mellado, S. Discenza, P. Lepage, S. Hawkins, F. Méchinaud, Alexandra Compagnucci, T. Ilmet, A. Mangano, H. Carreira, Andrew J. Pollard, G. Silva, L. Cerracchio, R. Sellers, Edward Handelsman, C. Floch, M. Lajeunesse, Stefano Vella, Thalita F. Abreu, N. Martinez-Allier, C. Florea, C. Newbould, I. Grosch-Wörner, M. F. Courcoux, Gert Warncke, I. Whyms, J. C. Gabaldi, T. Piening, F. Hoffman, V. Shah, B. Bucholz, S. Costa, G. Firtion, E. R. Stiehm, J. Palm, S. Deygoo, L. Rosado, V. Tournier, Y. Saïdi, M. Wigger, G. Vaudre, V. Lobato, E. Yeagley, A. B. Bohlin, Delane Shingadia, L. S. Spencer, M. Depala, G. Tardei, S. Akleh, S. Marks, S. Vasquez Bonilla, Stefania Bernardi, D. Costello, S. Segal, S. Gudowius, Saniyyah Mahmoudi, M. Debré, C. Borne, D. Melvin, S. Kaye, S. Johnson, Ellen G. Chadwick, Marie-Laure Chaix, H. Loeffler, G. Stringari, J. L. Jimenez, Arry Dieudonne, G. Notheis, J. Dodge, C. Nesel, D. Mecikovsky, Meredith G. Warshaw, Shunmay Yeung, C. De Bortoli, J. Shenton, R. de Groot, S. Forcat, M. A. Kelly, J. Usher, I. Falconi, M. Rein, D. Nayagam, R. Delgado Garcia, P. McMaster, J. Flynn, S. Rugina, Susan A. Fiscus, S. Liebeschuetz, A. Sorlini, G. Tatum, Magdalena Marczyńska, H. J. Laws, Paul Palumbo, Nigel Klein, E. Daghofer, D. Painter, D. Poalelungi, Anne A. Gershon, L. Martins, N. Pineda, Patricia M. Flynn, J. H. Darbyshire, Michael Hughes, Pim Brouwers, Guido Castelli-Gattinara, M. Byrne, J. Stroobant, G. Talero, C. Reed, D. Patel, F. Nganzali, J. F. Méritet, M. Elizabeth Smith, M. A. Muñoz Fernandez, K. Huck, G. Castelli Gattinara, M. L. Issac, S. Gaur, M. Johnson, K. Mohan, B. Ward, A. Cheng, M. Dunn, M. Frere, T. Alford, K. Doerholt, S. Storey, J. Smith, S. Cleto, A. Ferreira, J. Darbyshire, J. Johnson, A. Marion, P. Butler, K. M. Kim, H. Hichou, D. Casey, L. Farrelly, R. Draghicenoiu, Alessandra Viganò, M. F. Melo, S. Bellert, Jintanat Ananworanich, F. Ferreira, K. Sloper, Deenan Pillay, E. Ferguson, Karina Butler, D. Rivaux, A. D. Fernandez, M. Penin, V. Bennato, M. Filisetti, W. Tomosada, Daria Trabattoni, J. P. Aboulker, A. Diniz, Patricia Emmanuel, C. Rodier, Jorge Pinto, S. McDonagy, M. Goode, K. Swaminathan, H. Sprenger, L. Deveikis, L. Ball, E. André, Susan Laverty, John S. Lambert, F. Abaab, C. Hill, A. Menon, A. García Torre, T. Belger, Christoph Rudin, R. Neubauer, Cornelia Feiterna-Sperling, U. Wintergerst, B. Brody, Silvia Netescu, Ross E. McKinney, Yoann Riault, J. Galimand, G. Deluchi, J. Hobbs, K. Buckberry, C. Mazhude, S. Doshi, Maripat Toye, C. Ball, David M. Burger, A. Werthmann, R. Matusa, J. Wong, Joseph A. Church, M. Pourrat, K. Pfurtscheller, S. Seyboldt, R. Lawrence, M. Butler, D. Scott, T. Niehues, Katherine Luzuriaga, B. Pabst, R. Lakshman, M. Donohoe, A. Ortwin, M. Brusati, M. O’connell, W. Queiroz, M. P. Gomez, J. C. Roa, P. Rojo Conejo, A. De Rossi, C. Norgeux, A. Rochford, Linda Harrison, Tao Dong, W. Zenz, S. Donaghy, S. Mellul, L. M. Lira, Paula Britto, J. Romeiro, C. Taylor, J. Jackson Alvarez, Judith A. Guzman-Cottrill, J. Arias, Lynne M. Mofenson, D. Calo, I. Le Moal, J. Lujan-Zimmerman, T. Alchediak, C. Guérin, Ricardo H. Oliveira, Jonathan Cohen, D. Kwolfe, Ana Puga, L. Navarante, William T. Shearer, L. Angeli, Marc Lallemant, J. Bane, Niels Henrik Valerius, Ayesha Mirza, John F. Modlin, G. Rossetti, David Nadal, M. Acevedo-Flores, F. Shackley, S. Léonardo, E. Smidt, I. Jimenez Nacher, Margarita Silio, Geoffrey A. Weinberg, C. Galvez, F. Kakehasi, L. Fabregas, S. Moore, M. M. Mussi-Pinhata, M. O’connor, M. Diniz, M. Mardarescu, J. King, Sohail Rana, D. Johnson, J. M. Ferrari, Lisa M. Frenkel, T. Hastings, C. Wells, R. B. Van Dyke, G. Bowen, Claire Thorne, L. Sen, E. Hyland, L. Barrett, E Jungmann, Mobeen H. Rathore, D. Beniken, B. Sodiende, C. Ryan, A. Malheiro, Y. Peng, R. O’connell, A. Walsh, John L. Sullivan, A. Deveikis, P. Rice, A. Le Pelletier, A. Poziak |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
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| Zdroj: |
The Lancet Infectious Diseases; Vol 11 |
| ISSN: |
1473-3099 |
| DOI: |
10.1016/s1473-3099(10)70313-3 |
| Popis: |
Background Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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