1. Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection
- Author
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Michael, Kozal, Judith, Aberg, Gilles, Pialoux, Pedro, Cahn, Melanie, Thompson, Jean-Michel, Molina, Beatriz, Grinsztejn, Ricardo, Diaz, Antonella, Castagna, Princy, Kumar, Gulam, Latiff, Edwin, DeJesus, Mark, Gummel, Margaret, Gartland, Amy, Pierce, Peter, Ackerman, Cyril, Llamoso, Max, Lataillade, A, Wurcel, Yale School of Medicine [New Haven, Connecticut] (YSM), Icahn School of Medicine at Mount Sinai [New York] (MSSM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fundación Huésped [Buenos Aires], Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Federal University of Sao Paulo (Unifesp), IRCCS San Raffaele Scientific Institute [Milan, Italie], Georgetown University [Washington] (GU), Orlando Immunology Center, GlaxoSmithKline, Glaxo Smith Kline, GlaxoSmithKline [Research Triangle Park] (GSK ), ViiV Healthcare US, ViiV Healthcare [Brentford, UK], BRIGHTE Trial Team: P Cahn, L Cassetti, D O David, E Loiza, D Cecchini, S Lupo, M Martins, C Zala, A Carr, J McMahon, S De Wit, E Florence, C R Alves, J Andrade Neto, M Della Negra, R Diaz, B Grinsztejn, J Madruga, K Morejon, F Ribeiro, E Sprinz, M Murray, J Szabo, S Trottier, S Walmsley, J Ballesteros, F Zamora, C Beltran, C Chahin Anania, C Perez, M Wolff Reyes, J Velez, P M Girard, C Katlama, J-M Molina, D Neau, G Pialoux, I Poizot-Martin, F Raffi, D Salmon-Ceron, K Arastéh, A Baumgarten, J Bogner, M Hower, W Kern, D Schürmann, C Stephan, S Metallidis, V Paparizos, P Mallon, A Antinori, R Cauda, A Lazzarin, G Migliorino, C Mussini, G Orofino, G Rizzardini, P F Belaunzaran, R Cabello, J Duque Rodríguez, M Santoscoy-Gómez, S C Treviño, I Hoepelman, F Mendo, Y Pinedo Ramirez, M Parczewski, B Knysz, N Janeiro, F Maltez, L Preotescu, A Streinu-Cercel, G Latiff, I Mitha, J M Libre Codina, S Moreno Guillén, J Pineda, S M Hsieh, A Pozniak, J Aberg, J Bartczak, M Berhe, T Campbell, C Creticos, E DeJesus, V Drelichman, C Durand, J Eron, C Fichtenbaum, R Grossberg, S Gupta, F Haas, D Hagins, M Jain, M Kozal, P Kumar, J Lalezari, J Lennox, R Loftus, R Lubelchek, J McGowan, M McKellar, A Mills, J Morales-Ramirez, O Osiyemi, N Ramgopal, S Schrader, J Slim, P Tebas, M Thompson, W Towner, T Wilkin, A Wurcel, Malbec, Odile, Kozal, M., Aberg, J., Pialoux, G., Cahn, P., Thompson, M., Molina, J. -M., Grinsztejn, B., Diaz, R., Castagna, A., Kumar, P., Latiff, G., Dejesus, E., Gummel, M., Gartland, M., Pierce, A., Ackerman, P., Llamoso, C., Lataillade, M., Yale University School of Medicine, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Adult ,Male ,[SDV]Life Sciences [q-bio] ,Human immunodeficiency virus (HIV) ,HIV Infections ,Drug resistance ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Piperazines ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Drug Resistance, Multiple, Viral ,Randomized controlled trial ,law ,Humans ,Medicine ,Prodrugs ,030212 general & internal medicine ,Aged ,business.industry ,General Medicine ,Middle Aged ,Viral Load ,Virology ,Organophosphates ,CD4 Lymphocyte Count ,3. Good health ,[SDV] Life Sciences [q-bio] ,Clinical trial ,Multiple drug resistance ,Fostemsavir ,Anti-Retroviral Agents ,Multicenter study ,HIV-1 ,RNA, Viral ,Drug Therapy, Combination ,Female ,business - Abstract
International audience; Background: Among some patients with human immunodeficiency virus type 1 (HIV-1) infection who have undergone multiple antiretroviral therapies and have limited options for treatment, new classes of antiretroviral drugs with novel mechanisms of action are needed. Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor.Methods: In this ongoing phase 3 trial in 23 countries, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to their remaining treatment options. In the first cohort, we assigned (in a 3:1 ratio) patients who had the option of using at least one fully active, approved antiretroviral drug in at least one but no more than two antiretroviral classes to add either fostemsavir (at a dose of 600 mg twice daily) or placebo to their failing regimen for 8 days, followed by open-label fostemsavir plus optimized background therapy (randomized cohort). In the second cohort, patients who had no remaining antiretroviral options were started on open-label fostemsavir plus optimized background therapy on day 1 (nonrandomized cohort). The primary end point was the mean change in the HIV-1 RNA level from day 1 through day 8 in the randomized cohort.Results: A total of 371 patients were treated, including 272 in the randomized cohort and 99 in the nonrandomized cohort. At day 8, the mean decrease in the HIV-1 RNA level was 0.79 log10 copies per milliliter in the fostemsavir group and 0.17 log10 copies in the placebo group (P
- Published
- 2020
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