1768. Efficacy and Safety of Switching from Boosted-Protease Inhibitors (bPI) plus Emtricitabine/Tenofovir Disoproxil Fumarate (F/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: Week 96 Results of the Phase 3, Randomized, Non-Inferiority EMERALD Trial
Session: Oral Abstract Session: Optimizing HIV Treatment
Saturday, October 6, 2018: 11:00 AM
Room: S 156

Background: The QD STR D/C/F/TAF 800/150/200/10mg was non-inferior to bPI + F/TDF at 48 weeks in EMERALD. Efficacy and safety of D/C/F/TAF through wk 96 is presented.

Methods: EMERALD (NCT02269917) is a randomized, active controlled, open label, international, multicenter noninferiority trial. Virologically suppressed (VL<50c/mL for ≥2 mths) ART experienced (previous non-DRV VF allowed) HIV-1 infected adults were randomized (2:1) to switch to D/C/F/TAF or continue bPI + F/TDF over 48 wks. Patients could then continue on D/C/F/TAF or switch from bPI + F/TDF to D/C/F/TAF at wk 52 (Late switch, 44 wks D/C/F/TAF exposure) in a single arm extension phase until wk 96. The % of patients with virologic rebound (confirmed VL≥50c/mL) cumulative through wk 48 and wk 96 were primary and secondary endpoints, respectively.

Results: Of 1141 randomized and treated patients (58% had received ≥5 previous ARVs including screening ARVs; 15% had previous non-DRV VF), 1080 continued in the extension phase (N=728 D/C/F/TAF; N=352 late switch). Few patients had virologic rebound cumulative through wk 96 in the D/C/F/TAF arm (3.1%, 24/763). Virologic rebound occurred in 2.3% (8/352) in the late switch arm over 44 weeks D/C/F/TAF treatment. Many rebounders (14/24 and 2/8) resuppressed by wk 96. At wk 96 a high % of patients in the D/C/F/TAF arm (90.7%, 692/763) were suppressed (VL<50c/mL). In the late switch arm 93.8% (330/352) maintained virologic suppression after 44 weeks of treatment. No DRV, primary PI, TFV or FTC RAMs were seen post baseline. Few serious AEs and AE related discontinuations occurred in either arm (Table 1). Improvements in renal and bone parameters were maintained in the D/C/F/TAF arm and seen in the late switch arm (wk 52–96), with a small change in TC/HDL-C ratio (Table 1).
Conclusion: Switching to D/C/F/TAF maintained high virologic suppression rates (>90%) at wk 96 with no resistance development, and was well tolerated over 96 wks with bone, renal and lipid safety consistent with known TAF and cobicistat profiles. Efficacy and safety results in the late switch arm were consistent with wk 48 results in the D/C/F/TAF arm. D/C/F/TAF combines the efficacy and high genetic barrier to resistance of DRV with the safety benefits of TAF, even in patients with a history of non-DRV VF.

.

 

Joseph Eron Jr., MD1, Chloe Orkin, MBBCh2, Douglas Cunningham, DO3, Federcio Pulido, MD4, Frank Post, MD PhD5, Stéphane De Wit, MD6, Erkki Lathouwers, PhD7, Veerle Hufkens, MSc7, Romana Petrovic, MSc7, Erika Van Landuyt, MD7 and the EMERALD study group, (1)The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, (2)Department of Infection and Immunity, Royal London Hospital and Queen Mary University, Barts Health NHS Trust, London, United Kingdom, (3)Pueblo Family Physicians, Phoenix, AZ, (4)HIV Unit, Hospital 12 de Octubre, Madrid, Spain, (5)King's College Hospital NHS Foundation Trust, London, United Kingdom, (6)Saint-Pierre University Hospital, Université Libre de Bruxelles, Brusseks, Belgium, (7)Janssen Pharmaceutica NV, Beerse, Belgium

Disclosures:

J. Eron Jr., Gilead: Consultant and Grant Investigator , Consulting fee and Research grant . Janssen: Consultant , Consulting fee and Research grant .

C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor , Research grant and Research support .

D. Cunningham, Janssen: Investigator , Research grant . Gilead: Investigator , Research grant .

F. Pulido, Janssen: Consultant , Investigator and Scientific Advisor , Consulting fee , Research support and Speaker honorarium .

F. Post, Gilead: Consultant and Grant Investigator , Consulting fee and Grant recipient . Viiv: Grant Investigator , Grant recipient . Janssen: Consultant , Consulting fee . MSD: Consultant , Consulting fee .

S. De Wit, Janssen: Investigator , Research grant .

E. Lathouwers, Janssen: Employee and Shareholder , Salary .

V. Hufkens, Janssen: Employee and Shareholder , Salary .

R. Petrovic, Janssen R&D: Independent Contractor , Consulting fee .

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

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.