Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

AIDS. 2020 Apr 1;34(5):707-718. doi: 10.1097/QAD.0000000000002463.

Abstract

Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in AMBER (NCT02431247).

Methods: Treatment-naive, HIV-1-positive adults [screening plasma viral load ≥1000 copies/ml; CD4 cell count >50 cells/μl) were randomized (1 : 1) to D/C/F/TAF (N = 362) or D/C plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) (N = 363) over at least 48 weeks. After week 48, patients could continue on or switch to D/C/F/TAF in an open-label extension phase until week 96.

Results: At week 96, D/C/F/TAF exposure was 626 patient-years (D/C/F/TAF arm) and 109 patient-years (control arm post switch), week 96 virologic suppression (viral load <50 copies/ml; FDA-Snapshot, from baseline) was 85.1% (308/362) (D/C/F/TAF) and 83.7% (304/363) (control). Week 96 virologic failure (viral load ≥50 copies/ml; FDA-Snapshot) was 5.5% (20/362) and 4.4% (16/363), respectively. No darunavir, primary protease inhibitor or tenofovir resistance-associated mutations (RAMs) were observed post baseline. In one patient in each arm, an M184I and/or V RAM was detected. Few adverse event-related discontinuations (3% D/C/F/TAF; <1% control post switch) and no deaths occurred on D/C/F/TAF. Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the control arm post switch. Increases in total-cholesterol/high-density-lipoprotein--cholesterol rtio at week 96 were +0.25 versus baseline (D/C/F/TAF) and +0.24 versus switch (control).

Conclusion: At week 96, D/C/F/TAF resulted in high virologic response and low virologic failure rates, with no resistance development to darunavir or TAF/TDF. Bone, renal and lipid safety were consistent with known D/C/F/TAF component profiles. Control arm safety post switch was consistent with the D/C/F/TAF arm. AMBER week 96 results confirm the efficacy, high barrier to resistance and bone/renal safety benefits of D/C/F/TAF for treatment-naive patients.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenine / analogs & derivatives
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / therapeutic use
  • Cobicistat / therapeutic use
  • Darunavir / therapeutic use
  • Double-Blind Method
  • Drug Combinations
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Protease Inhibitors / administration & dosage*
  • Protease Inhibitors / therapeutic use
  • Tablets*
  • Tenofovir / therapeutic use
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Drug Combinations
  • Protease Inhibitors
  • Tablets
  • Tenofovir
  • tenofovir alafenamide
  • Emtricitabine
  • Adenine
  • Cobicistat
  • Darunavir

Associated data

  • ClinicalTrials.gov/NCT02431247