Portal de Periódicos da CAPES

Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

2019; Mary Ann Liebert, Inc.; Volume: 36; Issue: 1 Linguagem: Inglês

10.1089/aid.2019.0111

1931-8405

Erkki Lathouwers, Eric Wong, Kimberley Brown, Bryan Baugh, Anne Ghys, John Jezorwski, El Ghazi Mohsine, Erika Van Landuyt, Magda Opsomer, Sandra De Meyer, Christoph Stephan, Éric Florence, Linos Vandekerckhove, Bernard E. Van Beers, Jason Brunetta, Marina B. Klein, Daniel Murphy, Anita Rachlis, Sharon Walmsley, F. Ajana, Laurent Cotte, PM Girard, Christine Katlama, Jean‐Michel Molina, Isabelle Poizot‐Martin, François Raffi, D. Rey, Jacques Reynes, Elina Teicher, Yazdan Yazdanpanah, Keikawus Arastéh, Markus Bickel, Johannes R. Bogner, Stefan Eßer, Gerd Faetkenheuer, Heiko Jessen, W. Kern, J Rockstroh, Christoph D. Spinner, HJ Stellbrink, Albrecht Stoehr, Andrea Antinori, Francesco Castelli, Antonio Chirianni, Andrea De Luca, Antonio Di Biagio, Massimo Galli, Adriano Lazzarin, Franco Maggiolo, Renato Maserati, C Mussini, Aleksander Garlicki, Jacek Gąsiorowski, Waldemar Halota, Andrzéj Horban, Miłosz Parczewski, Anna Piekarska, Elena Belonosova, О. А. Чернова, Natalya V. Dushkina, Vyacheslav Kulagin, E. P. Ryamova, А A Shuldyakov, Наталия Владимировна Сизова, O Tsybakova, Evgeny Voronin, A. N. Yakovlev, Antonio Antela, José Ramón Arribas, Juan Berenguer, José L. Casado, Vicente Estrada, MJ Galindo, M Garcia Del Toro, JM Gatell, Miguel Górgolas, Félix Gutiérrez, MDM Gutierrez, Eugènia Negredo, Juan A. Pineda, Daniel Podzamczer, Joaquín Portilla, Antonio Rivero, Rafael Rubio, Pompeyo Viciana, Ignacio de los Santos, Amanda Clarke, BG Gazzard, MA Johnson, Chloe Orkin, Iain Reeves, Laura Waters, Paul Benson, Laveeza Bhatti, Fritz Bredeek, Gordon E Crofoot, David Cunningham, E DeJesus, Joseph J. Eron, Franco Felizarta, Renato Franco, Joel E. Gallant, D Hagins, Kenneth R. Henry, Dushyantha Jayaweera, Christopher Lucasti, Claudia Martorell, C McDonald, Joseph P. McGowan, Anthony Mills, Javier O Morales-Ramirez, D Prelutsky, Moti Ramgopal, Bruce Rashbaum, Peter Ruane, Jihad Slim, Aimee Wilkin, James DeVente, Christoph Stephan, Éric Florence, Michel Moutschen, Eric Van Wijngaerden, Linos Vandekerckhove, Bernard E. Van Beers, Jason Brunetta, Brian Conway, Marina B. Klein, Daniel Murphy, Anita Rachlis, Stephen D. Shafran, Sharon Walmsley, F. Ajana, Laurent Cotte, PM Girard, Christine Katlama, Jean‐Michel Molina, Isabelle Poizot‐Martin, François Raffi, D. Rey, Jacques Reynes, Elina Teicher, Yazdan Yazdanpanah, Jacek Gąsiorowski, Waldemar Halota, Andrzéj Horban, Anna Piekarska, Anita Witor, José Ramón Arribas, Ignacio Valero, Juan Berenguer, José L. Casado, JM Gatell, Félix Gutiérrez, MJ Galindo, MDM Gutierrez, JA Iribarren, Hernando Knobel, Eugènia Negredo, Juan A. Pineda, Daniel Podzamczer, Joaquín Portilla, Federico Pulido, C Ricart, Antonio Rivero, I Santos Gil, Anders Blaxhult, Leo Flamholc, Magnus Gisslén, Anders Thalme, Jan Fehr, Andri Rauch, Marcel Stoeckle, Amanda Clarke, BG Gazzard, MA Johnson, Chloe Orkin, Frank A. Post, Andrew Ustianowski, Laura Waters, Joseph I. Bailey, Paul Benson, Laveeza Bhatti, Indira Brar, U. Fritz Bredeek, Cynthia Brinson, Gordon E Crofoot, David Cunningham, E DeJesus, C Dietz, Robin Dretler, Joseph J. Eron, Franco Felizarta, Carl J. Fichtenbaum, Joel E. Gallant, Joseph Gathe, D Hagins, S Henn, KW Henry, Gregory Huhn, Mamta K. Jain, Christopher Lucasti, Claudia Martorell, C McDonald, Anthony Mills, Javier O Morales-Ramirez, Karam Mounzer, Ronald Nahass, H Olivet, Olayemi Osiyemi, D Prelutsky, Moti Ramgopal, Bruce Rashbaum, Gary Richmond, Peter Ruane, A Scarsella, Anita Scribner, Peter Shalit, David Shamblaw, Jihad Slim, K. Tashima, Gene W. Voskuhl, D Ward, Aimee Wilkin, Jerome De Vente,

HIV Research and Treatment

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL <50 copies/mL) in EMERALD. Through week 48 across both studies, no darunavir, primary PI, or tenofovir resistance-associated mutations (RAMs) were observed in HIV-1 viruses of 1,125 participants receiving D/C/F/TAF or 629 receiving boosted darunavir plus emtricitabine/tenofovir-disoproxil-fumarate. In AMBER, the nucleos(t)ide analog reverse transcriptase inhibitor (N(t)RTI) RAM M184I/V was identified in HIV-1 of one participant during D/C/F/TAF treatment. M184V was detected pretreatment as a minority variant (9%). In EMERALD, in participants with prior VF and genoarchive data (N = 140; 98 D/C/F/TAF and 42 control), 4% had viruses with darunavir RAMs, 38% with emtricitabine RAMs, mainly at position 184 (41% not fully susceptible to emtricitabine), 4% with tenofovir RAMs, and 21% ≥ 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response.