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.

Erika Van Landuyt, Erkki Lathouwers, Veerle Hufkens, Magda Opsomer, Kimberley Brown, Romana Petrovic, Joseph J Eron, Chloe Orkin, Douglas Cunningham, Federico Pulido, Frank A Post, Stéphane De Wit, John Jezorwski

Journal: Antiviral research 2020;170():104543

PMID: 31279073

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.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Address: University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: [email protected].; Queen Mary University, London, UK.; Pueblo Family Physicians, Phoenix, AZ, USA.; HIV Unit, Hospital 12 de Octubre, imas12, UCM, Madrid, Spain.; King's College Hospital NHS Foundation Trust, London, United Kingdom.; Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.; Janssen Pharmaceutica NV, Beerse, Belgium.; Janssen Research & Development, Pennington, NJ, USA.; Institute of Tropical Medicine, Antwerp, Belgium.; Infectious Diseases department, Liège University Hospital, Liège, Belgium.; Department of General Internal Medicine, University Hospitals, KU Leuven - University of Leuven, Belgium.; Ghent University and Ghent University Hospital, Ghent, Belgium.; AIDS Reference center, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.; Maple Leaf Medical Clinic, Toronto, Canada.; Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada.; Division of Infectious Diseases, Faculty of Medicine, McGill University Health Centre, Montreal, QC, Canada.; Institut national de santé publique du Québec, Montréal, QC, Canada.; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University of Alberta, Edmonton, Canada.; University Health Network, Toronto, ON, Canada.; Infectious Diseases Department, Tourcoing Hospital, Tourcoing, France.; Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France.; University Pierre & Marie Curie, Paris, France.; HIV Clinical Research Unit, Hôpital pitié-Salpêtrière, Paris, France.; Department of Infectious Diseases, St-Louis Hospital APHP, University of Paris Diderot, Paris, France.; Clinical Immuno-Hematology Department, Aix-Marseille University, Sainte-Marguerite University Hospital and Inserm U912, Marseille, France.; CHU Hôtel Dieu, Nantes, France.; Le Trait d'Union, HIV-Infection Care Center, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.; Montpellier University Hospital, Montpellier, France.; Infectious Diseases Department, APHP, Hôpital Bicêtre, Le Kremlin Bicêtre, France.; 14AP-HP Bichat, Paris, France.; Independent Laboratory for Monitoring Infections among Drug Users at the Department of Infectious Diseases, Liver Disease and Acquired Immune Deficiencies, Wroclaw Medical University, Poland.; Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Bydgoszcz, Poland.; Medical University of Warsaw, Department for Adult's Infectious Diseases, Warsaw, Poland.; Department of Infectious Diseases and Hepatology , Medical University of Lodz, Lodz, Poland.; Regional Hospital, Out-Patient's Clinic for Immune Deficiency, Chorzów, Poland.; Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.; Department of La Paz Hospital, Madrid, Spain.; Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.; Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.; Infectious Diseases Department, HCB, Barcelona, Spain.; Infectious Diseases Unit, Hospital Universitario de Elche, Alicante, Spain.; Hospital Clínico Universitario de Valencia, Valencia, Spain.; Department of Infectious Diseases, HIV Infection Unit, Hospital de la Santa Creu i Sant Pau, Institut de Recerca del Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.; Hospital Universitario Donostia, San Sebastián, Spain.; Hospital del Mar, Universitat Autonòma de Barcelona, Barcelona, Spain.; Lluita contra la Sida Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain.; Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain.; dIDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain.; Medicina Interna, Hospital General Universitario de Alicante, Alicante, Spain.; Department of Microbiology, School of Medicine, University of Valencia, Spain.; Infectious Diseases Unit, Hospital Universitario Reina Sofía, Instituto Maimonides de Investigación Biomedica de Córdoba IMIBIC Cordoba University, Cordoba, Spain.; Unidad de Enfermedades Infecciosas, Hospital Universitario de la Princesa, Madrid, Spain.; Department of Infectious Diseases, Venhälsan, Södersjukhuset, Stockholm, Sweden.; Department of Infectious Diseases, Malmö University Hospital, 205 02 Malmö, Sweden.; Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Department of Infectious Diseases, Bern University Hospital Inselspital, University of Bern, Bern, Switzerland.; Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland.; Claude Nicol Centre, Royal Sussex County Hospital, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.; St. Stephen's Centre, Department of HIV/Genito-Urinary Medicine, Chelsea and Westminster Hospital, London, UK.; Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, UK.; King's College Hospital NHS Foundation Trust, London, UK.; Regional Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK.; University College London Hospital, London, UK.; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Be Well Medical, Berkley, MI, USA.; AIDS Healthcare Foundation, Beverly Hills, California, USA.; Henry Ford Hospital, Detroit, MI, USA.; Metropolis Medical PC, San Francisco, CA, USA.; Central Texas Clinical Research, Austin, TX, USA.; The Crofoot Research Center, Houston, TX, USA.; University of North Carolina School of Medicine, Chapel Hill, NC, USA.; Orlando Immunology Center, Orlando, FL, USA.; HIV Medicine, Kansas City Free Health Clinic, Kansas City, MO, USA.; Infectious Disease Specialists of Atlanta, Atlanta, GA, USA.; Private Practice, 3535 San Dimas Street, Suite 24, Bakersfield, CA 93301, USA.; University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Southwest CARE Center, Santa Fe, New Mexico, USA.; Therapeutic Concepts, Houston, TX, USA.; Georgia Department of Public Health, Coastal Health District, Chatham Care Center, Savannah, GA, USA.; Whitman-Walker Health, Washington, DC, USA.; Department of Medicine, University of Minnesota Washington University School of Medicine, St. Louis, Missouri, USA.; Ruth M. Rothstein CORE Center, Chicago, IL, USA.; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.; South Jersey Infectious Disease, Somers Point, NJ, USA.; Infectious Disease and The Research Institute, Springfield, MA, USA.; Tarrant County Infectious Disease Associates, Fort Worth, TX, USA.; Southern California Men's Medical Group, Los Angeles, California, USA.; Clinical Research Puerto Rico Inc., San Juan, Puerto Rico, USA.; Philadelphia FIGHT, 1233 Locust Street, 3rd Floor, Philadelphia, PA, USA.; ID Care, Hillsborough, NJ, USA.; Community Research Initiative of New England, Boston, USA.; Triple O Research Institute PA, West Palm Beach, FL, USA.; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.; Midway Immunology Center, Fort Pierce, FL, USA.; Capital Medical Associates, Washington, DC, USA.; Broward General Medical Center, Fort Lauderdale, FL, USA.; Ruane Clinical Research Group, Los Angeles, CA, USA.; Pacific Oaks Medical Group, Beverly Hills, CA, USA.; DCOL Center for Clinical Research, Longview, TX, USA.; Peter Shalit MD and Associates, 901 Boren Avenue, Suite 850, Seattle, WA, 98104, USA.; La Playa Medical Group, San Diego, CA, USA.; Department of Infectious Diseases, Seton Hall University, NJ, USA.; The Miriam Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.; AIDS Arms, Inc., Dallas, TX, USA.; Dupont Circle Physicians Group, Washington, DC, USA.; Wake Forest School of Medicine, Winston-Salem, NC, USA.; Living Hope Foundation, Long Beach, CA, USA.
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