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

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RESEARCH PRODUCT

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

Douglas Cunningham D. Ward Mamta K. Jain Faiza Ajana Magda Opsomer Anita Rachlis Sharon Walmsley Frank A. Post Anders Blaxhult Amanda Clarke M. J. Galindo Marcel Stoeckle P.-m. Girardy Karam Mounzer David Shamblaw U. F. Bredeek L. Bhatti J. J. Eron Andrew Ustianowski Mar Gutierrez John Jezorwski Javier O Morales-ramirez Antonio Rivero M.a. Johnson Gatell Jm Erika Van Landuyt Stéphane De Wit A. Wilkin Laurent Cotte Cheryl Mcdonald D. Murphy Cynthia Brinson Romana Petrovic Olayemi Osiyemi J. De Vente I. Poizot-martin Juan Berenguer Robin Dretler J. Bailey B. Rashbaum Moti Ramgopal A. Scribner Yazdan Yazdanpanah Eric Florence A. Piekarska Brian Gazzard Chloe Orkin W. Halota Gary Richmond Jacques Reynes C. Ricart C. Lucasti Ignacio Pérez-valero Jason Brunetta S. Shafran S. Shafran Daniel Podzamczer Franco Antonio Felizarta Claudia Martorell F. Post Peter Ruane Edwin Dejesus J. Portilla Sogorb C. Orkin K. Tashima Federico Pulido Bernard Vandercam F. Pulido José L. Casado Christine Katlama Kimberley Brown J Gasiorowski A. Witor Joseph J. Eron Brian Conway Andri Rauch Jose R. Arribas Michel Moutschen H. Olivet A. Scarsella Leo Flamholc A. Horban D. Cunningham Ronald Nahass Félix Gutiérrez G. Huhn W.k. Henry A. Thalme S De Wit Jan Fehr Debbie Hagins José Antonio Iribarren J.-m. Molina S. Henn F Raffi Juan A. Pineda Marina B. Klein Eugenia Negredo Hernando Knobel J. Slim P. Benson L. Waters E. Teicher Linos Vandekerckhove Craig A. Dietz Magnus Gisslén Joel E. Gallant J. Gathe P. Shalit D. Prelutsky G. Voskuhl D. Rey E. Van Wijngaerden Anthony Mills Erkki Lathouwers Carl J. Fichtenbaum I. Brar Gordon Crofoot Veerle Hufkens I. Santos Gil

subject

Male DOLUTEGRAVIR Sustained Virologic Response HIV Infections Gastroenterology chemistry.chemical_compound 0302 clinical medicine Medicine and Health Sciences Emtricitabine 030212 general & internal medicine Pharmacology & Pharmacy Darunavir 0303 health sciences Alanine Drug Substitution Cobicistat Emtricitabine Tenofovir Disoproxil Fumarate Drug Combination Lamivudine Antiretrovirals Middle Aged Viral Load OPEN-LABEL 3. Good health WEIGHT-GAIN Drug Combinations Treatment Outcome Dolutegravir NON-INFERIORITY Female Safety Viral load Life Sciences & Biomedicine medicine.drug Tablets Adult medicine.medical_specialty Efficacy Anti-HIV Agents RITONAVIR Emtricitabine TENOFOVIR ALAFENAMIDE LAMIVUDINE Tenofovir alafenamide Single-tablet regimen 03 medical and health sciences Internal medicine Virology medicine VIH (Virus)Humans Switch study Protease Inhibitors Tenofovir Darunavir Aged Pharmacology Science & Technology 030306 microbiology business.industry HIV (Viruses)Adenine Darunavir/cobicistat/emtricitabine/TAF Antiretroviral agents COBICISTAT MAINTENANCE chemistry [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie HIV-1 Ritonavir Cobicistat [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie business RESISTANCE

description

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. ispartof: ANTIVIRAL RESEARCH vol:170 ispartof: location:Netherlands status: published

year	journal	country	edition	language
2019-10-01

10.1016/j.antiviral.2019.104543 http://hdl.handle.net/2445/171213