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

作者：Chloe Orkin, Joseph J. Eron, Jürgen K. Rockstroh, Daniel Podzamczer, Stefan Eßer, Linos Vandekerckhove, Erika Van Landuyt, Erkki Lathouwers, Veerle Hufkens, John Jezorwski, Magda Opsomer · 发表于：AIDS · 年份：2019 · DOI：10.1097/qad.0000000000002463 · 被引用次数：37 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、HIV-related health complications and treatments

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 swit...