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 - Archive ouverte HAL Access content directly
Journal Articles Antiviral Research Year : 2019

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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I.Santos Gil
  • Function : Author
Jason Brunetta
  • Function : Author
Faiza Ajana
  • Function : Author
  • PersonId : 950872
Laurent Cotte
  • Function : Author
  • PersonId : 937111
Christine Katlama
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  • PersonId : 927384
Francois Raffi
  • Function : Author
  • PersonId : 931385
David Rey
  • Function : Author
Andrzej Horban
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  • PersonId : 1027563
Eugenia Negredo
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  • PersonId : 876614
Margaret Johnson
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  • PersonId : 890131
Paul Benson
  • Function : Author
Indira Brar
  • Function : Author
Ulf Bredeek
  • Function : Author
Franco Felizarta
  • Function : Author
Joel Gallant
  • Function : Author
Joseph Gathe
  • Function : Author
Debbie Hagins
  • Function : Author
Sarah Henn
  • Function : Author
Gregory D Huhn
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Karam Mounzer
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Ronald Nahass
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Jihad Slim
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Gene Voskuhl
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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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hal-02615274 , version 1 (22-05-2020)

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Attribution - NonCommercial - NoDerivatives - CC BY 4.0

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