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 A 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 B 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 D 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 J Ward (97) , Aimee Wilkin (98)

1 UNC - University of North Carolina [Chapel Hill]
2 QMUL - Queen Mary University of London
3 Pueblo Family Physicians
4 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
5 KCH - King's College Hospital
6 ULB - Université libre de Bruxelles
7 Janssen Pharmaceutica [Beerse]
8 Janssen Research & Development
9 ITM - Institute of Tropical Medicine [Antwerp]
10 University Liege - Department of Infectious and Parasitic Diseases
11 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
12 Living Hope Foundation
13 Ghent University Hospital
14 Cliniques Universitaires Saint-Luc [Bruxelles]
15 Maple Leaf Clinic
16 Vancouver Infectious Diseases Centre
17 McGill University = Université McGill [Montréal, Canada]
18 University of Toronto
19 Sunnybrook Health Sciences Centre
20 University of Alberta
21 University Health Network
22 Services des maladies infectieuses [Tourcoing]
23 Hôpital de la Croix-Rousse [CHU - HCL]
24 SU - Sorbonne Université
25 CHU Pitié-Salpêtrière [AP-HP]
26 Service de maladies infectieuses et tropicales [Saint-Louis]
27 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
28 CHU Nantes - Centre hospitalier universitaire de Nantes
29 CHU Strasbourg
30 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
31 Service de Maladies Infectieuses et Tropicales [CHU Bicêtre]
32 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
33 UWr - University of Wrocław [Poland]
34 Faculty of Medicine [Bydgoszcz, Poland]
35 Medical University of Warsaw - Poland
36 MUL - Medical University of Łódź
37 Regional Hospital [Chorzow, Poland]
38 La Paz Hospital, IdiPAZ
39 Hospital General Universitario "Gregorio Marañón" [Madrid]
40 Hospital Universitario Ramón y Cajal [Madrid]
41 Infectious Diseases Service, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.
42 Hospital Universitario de Elche
43 Hospital Universitario de Valencia
44 Hospital de la Santa Creu i Sant Pau
45 Donostia Hospital Universitario San Sebastian
46 IMIM-Hospital del Mar
47 UAB - Universitat Autònoma de Barcelona
48 Hospital Universitario de Valme
49 Hospital Universitari de Bellvitge
50 UV - Universitat de València
51 Hospital Universitario Reina Sofía
52 Hospital Universitario de La Princesa
53 Karolinska Institutet, Södersjukhuset
54 Skane University Hospital [Malmo]
55 GU - University of Gothenburg
56 Karolinska University Hospital [Stockholm]
57 University hospital of Zurich [Zurich]
58 Inselspital - Bern University Hospital [Berne]
59 University Hospital Basel [Basel]
60 Royal Sussex County Hospital
61 Chelsea and Westminster Hospital
62 North Manchester General Hospital
63 UCL - University College of London [London]
64 Johns Hopkins University School of Medicine [Baltimore]
65 Be Well
66 AIDS healthcare foundation [California]
67 Henry Ford Hospital
68 Metropolis Medical
69 Central Texas Clinical Research
70 The Crofoot Research Center
71 Orlando Immunology Center
72 Kansas City Free Health Clinic
73 UC - University of Cincinnati
74 University of Minnesota System
75 University of Texas Southwestern Medical Center
76 South Jersey Infectious Disease
77 Infectious Disease
78 Tarrant County Infectious Disease Associates
79 Southern California Men’s Medical Group
80 Clinical Research Puerto Rico Inc
81 Philadelphia FIGHT
82 ID care
83 Community Research Initiative of New England
84 Triple O Research Institute PA
85 Washington University School of Medicine in St. Louis
86 Midway Immunology Center
87 Capital Medical Associates
88 Broward General Medical Center
89 Ruane Clinical Research Group
90 Pacific Oaks Medical Group
91 DCOL Center for Clinical Research
92 Peter Shalit MD and Associates
93 La Playa Medical Group
94 Seton Hall University
95 Warren Alpert Medical School of Brown University
96 AIDS Arms, Inc
97 Dupont Circle Physicians Group
98 Wake Forest School of Medicine [Winston-Salem]

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.

Keywords: Darunavir/cobicistat/emtricitabine/TAF; Single-tablet regimen; Safety; Efficacy; Switch study

Domains: Life Sciences [q-bio]; Santé publique et épidémiologie

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, 2019, 170, pp.104543. ⟨10.1016/j.antiviral.2019.104543⟩. ⟨hal-02615274⟩