1689b. Week 48 results of EMERALD: A Phase 3, randomized, non-inferiority study evaluating the efficacy and safety of switching from boosted-protease inhibitors (bPI) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) regimens to the once daily (QD), single-tablet regimen (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in virologically-suppressed, HIV-1-infected adults
Session: Oral Abstract Session: HIV: Modern ART
Friday, October 6, 2017: 3:18 PM
Room: 07AB

Background: EMERALD is evaluating the efficacy and safety of switching from bPI + FTC/TDF regimens (control) to D/C/F/TAF 800/150/200/10mg in virologically suppressed, HIV-1-infected adults. We present Wk 48 primary results.

Method: EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter, parallel-group, non-inferiority trial. Virologically suppressed (viral load [VL]<50c/mL for ≥2months), HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue control. The FDA-stipulated primary endpoint was non-inferiority of D/C/F/TAF vs control regarding % virologic rebound (confirmed VL≥50c/mL or premature discontinuations with last VL≥50c/mL) cumulative through Wk 48 (4% margin).

Result: 1141 patients were randomized and treated (N=763 D/C/F/TAF; N=378 control); median age 46; 18% women; 76% white; 58% on >2 previous ARVs (prior to screening regimen); 15% with previous non DRV virologic failure (VF).

Virologic rebound through Wk 48 was non-inferior for D/C/F/TAF (2.5%; n=19) vs control (2.1%; n=8) (D0.4%, 95%CI: –1.5%; 2.2%; p<0.001). Most rebounders (12/19 [63%] vs 4/8 [50%]) resuppressed by Wk 48 without change in therapy.

Wk 48 virologic suppression rates (VL<50c/mL; FDA Snapshot) were 94.9% vs 93.7% (D1.2%, 95%CI: −1.7%;4.1%) and VF rates (VL≥50c/mL; Snapshot) were 0.8% vs 0.5% (D0.3%, 95%CI: −0.7%;1.2%), with no discontinuations for VF. No resistance-associated mutations related to any study drug were observed.

Adverse events (AEs) were similar between arms: AE-related discontinuations (1.4% vs 1.3%); grade 3-4 AEs (6.8% vs 8.2%); serious AEs (4.6% vs 4.8%); and no deaths. Renal and bone parameters favored D/C/F/TAF vs control. TC and LDL-C slightly favored control vs D/C/F/TAF, with no clinically significant difference in TC/HDL-C ratio between arms (Table 1).

Conclusion: Percentage of virologic rebound after switching to D/C/F/TAF was non-inferior to control cumulative through Wk 48, with high suppression rates (94.9%), no resistance development, better bone and renal safety parameters and similar TC/HDL-C ratio. D/C/F/TAF maintains the high genetic barrier to resistance of darunavir with the safety advantages of TAF, even in patients with a history of non DRV VF.

Table 1: Changes from baseline at Week 48 in renal, lipid and bone parameters

 

 

Chloe Orkin, MBBCh1, Jean-Michel Molina, MD2, Joel Gallant, MD, MPH, FIDSA3, Eugenia Negredo, MD PhD4, Joseph Gathe, MD5, Joseph Eron Jr., MD6, Erika Van Landuyt, MD7, Erkki Lathouwers, PhD7, Veerle Hufkens, MSc7, Romana Petrovic, MSc7, Magda Opsomer, MD7 and EMERALD Study Group, (1)Department of Infection and Immunity, Royal London Hospital and Queen Mary University, Barts Health NHS Trust, London, United Kingdom, (2)University of Paris Diderot and Hôpital Saint-Louis, Paris, France, (3)Southwest CARE Center, Santa Fe, NM, (4)Germans Trias i Pujol University Hospital, Badalona, Spain, (5)Plaza Medical Center, Houston, TX, (6)Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, (7)Janssen Pharmaceutica NV, Beerse, Belgium

Disclosures:

C. Orkin, Janssen Pharmaceuticals: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Speaker honorarium and Travel bursary to attend conference
MSD: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Speaker honorarium and Travel bursary to attend conference
Viiv Healthcare: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Speaker honorarium and Travel bursary to attend conference
Gilead Sciences: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant , Speaker honorarium and Travel bursary to attend conference

J. M. Molina, Merck / Gilead: Scientific Advisor , Research grant
Janssen / Viiv / BMS / Teva: Scientific Advisor , Speaker honorarium
Gilead: Speaker's Bureau , Speaker honorarium

J. Gallant, Janssen Therapeutics: Investigator , Research support

E. Negredo, Janssen: Board Member , Scientific Advisor and Speaker's Bureau , Speaker honorarium

J. Gathe, Janssen: Consultant and Investigator , Research grant and Speaker honorarium

J. Eron Jr., Janssen: Consultant and Grant Investigator , Consulting fee and Grant recipient

E. Van Landuyt, Janssen: Employee and Shareholder , Salary

E. Lathouwers, Janssen: Employee and Shareholder , Salary

V. Hufkens, Janssen: Employee and Shareholder , Salary

R. Petrovic, Janssen: Employee and Shareholder , Salary

M. Opsomer, Janssen: Employee and Shareholder , Salary

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