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Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Joseph Eron 1 Chloe Orkin 2 Douglas Cunningham 3 Federico Pulido 4 Frank Post 5 Stéphane De Wit 6 Erkki Lathouwers 7 Veerle Hufkens 7 John Jezorwski 8 Romana Petrovic 7 Kimberley Brown 7 Erika Van Landuyt 7 Magda Opsomer 7 E. Florence 9 M. Moutschen 10 E.Van Wijngaerden 11 I.Santos Gil J.De Vente 12 Linos Vandekerckhove 13 Bernard Vandercam 14 Jason Brunetta 15 Brian Conway 16 Marina Klein 17 Donald Murphy 18 Anita Rachlis 19 Stephen Shafran 20 Sharon Walmsley 21 Faiza Ajana 22 Laurent Cotte 23 P-M Girardy 24 Christine Katlama 25 Jean Michel Molina 26 Isabelle Poizot-Martin 27 Francois Raffi 28 David Rey 29 Jacques Reynes 30 Elina Teicher 31 Yazdan Yazdanpanah 32 Jacek Gasiorowski 33 Waldemar Halota 34 Andrzej Horban 35 Anna Piekarska 36 Adam Witor 37 Jose R Arribas 38 Ignacio Perez-Valero 38 Juan Berenguer 39 Jl Casado 40 Jose Gatell 41 Félix Gutiérrez 42 Maria-José Galindo 43 Maria del Mar Gutierrez 44 José Antonio Iribarren 45 Hernando Knobel 46 Eugenia Negredo 47 Juan Pineda 48 Daniel Podzamczer 49 J.Portilla Sogorb 4 C Ricart 50 Antonio Rivero 51 Ignacio Santos-Gil 52 Anders Blaxhült 53 Leo Flamholc 54 Magnus Gisslén 55 Anders Thalme 56 Jan Fehr 57 Andri Rauch 58 Marcel Stoeckle 59 Amanda Clarke 60 Brian Gazzard 61 Margaret Johnson 2 Andrew Ustianowski 62 Laura Waters 63 Justin R Bailey 64 Paul Benson 65 Laveeza Bhatti 66 Indira Brar 67 Ulf Bredeek 68 Cynthia Brinson 69 Gordon Crofoot 70 Edwin Dejesus 3 Craig Dietz 71 Robin Dretler 72 Franco Felizarta Carl Fichtenbaum 73 Joel Gallant Joseph Gathe Debbie Hagins Sarah Henn Wk Henry 74 Gregory Huhn Mamta Jain 75 Christopher Lucasti 76 Claudia Martorell 77 Cheryl Mcdonald 78 Anthony Mills 79 Javier Morales-Ramirez 80 Karam Mounzer 81 Ronald Nahass 82 Hannah Olivet 83 Olayemi Osiyemi 84 David Prelutsky 85 Moti Ramgopal 86 Bruce Rashbaum 87 Gary Richmond 88 Peter Ruane 89 Anthony Scarsella 90 Anita Scribner 91 Peter Shalit 92 David Shamblaw 93 Jihad Slim 94 Karen Tashima 95 Gene Voskuhl 96 Douglas Ward 97 Aimee Wilkin 98
Abstract : Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
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Joseph Eron, Chloe Orkin, Douglas Cunningham, Federico Pulido, Frank Post, et al.. Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1. Antiviral Research, Elsevier Masson, 2019, 170, pp.104543. ⟨10.1016/j.antiviral.2019.104543⟩. ⟨hal-02615274⟩

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