Background: D/C/F/TAF, a once-daily, single-tablet regimen containing darunavir (D 800mg), cobicistat (C 150mg), emtricitabine (F 200mg) and tenofovir alafenamide (TAF 10mg), is undergoing investigation in two Phase 3 studies, EMERALD (NCT02269917) and AMBER (NCT02431247).
Methods: EMERALD, a randomized (2:1), open-label, international, multicenter, parallel-group, non-inferiority, 48-week study, is evaluating the efficacy and safety of switching to D/C/F/TAF vs continuing a boosted protease inhibitor plus emtricitabine/TDF (control) in patients who are virologically suppressed [viral load (VL)< 50c/mL] for ≥2 months. FDA-stipulated primary endpoint is proportion with cumulative virologic rebound (confirmed VL≥50c/mL or premature discontinuations, with last VL≥50c/mL) through Week 48 (non-inferiority margin=4%). Pre-planned Week 24 interim results are presented.
Results: 1141 patients were randomized and treated (N=763 D/C/F/TAF vs N=378 control). Baseline characteristics: median age 46; 18% women; 25% non-white (21% black); 10% CD4+< 350 cells/mm3; 71%, 22%, and 8% on darunavir, atazanavir and lopinavir, respectively (15% on cobicistat). Cumulative virologic rebound was 1.8% (n=14 D/C/F/TAF) vs 2.1% (n=8 control), of which 10/14 and 5/8 respectively, resuppressed (< 50c/mL) by Week 24; there were no confirmed rebounds ≥200c/mL. At Week 24, FDA snapshot analysis showed virologic suppression (VL< 50c/mL) was 96.3% (D/C/F/TAF) and 95.5% (control), and virologic failure occurred in 0.5% and 0.8%, respectively, with no discontinuations for virologic failure and no detected resistance to any study drug.
Safety was similar between arms through 24 weeks, with low incidences of Grade 3-4 adverse events (AEs) (D/C/F/TAF 4.5% vs control 4.5%), serious AEs (2.6% vs 3.2%), and treatment discontinuations (overall, 2.9% vs 2.9%; due to AEs, 1.4% vs 1.1%). The most common AEs (≥5% both arms) were: nasopharyngitis (7.6% vs 6.6%), URI (6.3% vs 6.3%), vitamin D deficiency (5.5% vs 5%). There were no deaths. Total cholesterol/HDL-cholesterol ratios were similar between arms, with minimal changes from baseline. Changes from baseline in renal safety parameters were consistent with known profiles of the individual D/C/F/TAF components; Mean ΔeGFR (cystatin-C clearance by CKD-EPI): +0.3mL/min/1.73m² (D/C/F/TAF) vs. -1.0mL/min/1.73m² (control).
Conclusions: In virologically suppressed adults, switching to once-daily D/C/F/TAF was well tolerated, resulted in a low cumulative virologic rebound rate, and a high virologic suppression rate through 24 weeks.