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 Res. 2019 Oct;170:104543. doi: 10.1016/j.antiviral.2019.104543. Epub 2019 Jul 4.

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.

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

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Alanine
  • Anti-HIV Agents / therapeutic use*
  • Cobicistat / therapeutic use
  • Darunavir / therapeutic use
  • Drug Combinations*
  • Drug Substitution*
  • Emtricitabine / therapeutic use
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / therapeutic use
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Humans
  • Male
  • Middle Aged
  • Protease Inhibitors / therapeutic use*
  • Sustained Virologic Response
  • Tablets / therapeutic use
  • Tenofovir / analogs & derivatives
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Drug Combinations
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
  • Protease Inhibitors
  • Tablets
  • Tenofovir
  • tenofovir alafenamide
  • Emtricitabine
  • Adenine
  • Cobicistat
  • Alanine
  • Darunavir