LB4. A Phase 3, Randomized, Controlled Clinical Trial of Bictegravir in a Fixed-Dose Combination, B/F/TAF, vs. ABC/DTG/3TC in Treatment-Naïve Adults at Week 96
Authors: Wohl David A , Yazdanpanah Yazdan , Baumgarten Axel , Clarke Amanda , Thompson Melanie , Brinson Cynthia , Hagins Debbie , Ramgopal Moti , Antinori Andrea , Wei Xuelian , White Kirsten , Collins Sean , Cheng Andrew , Quirk Erin , Martin Hal 
Published: November 2018

Abstract

Background
Bictegravir (B), a potent INSTI with a high barrier to resistance, is coformulated with emtricitabine (F) and tenofovir alafenamide (TAF) as the FDA-approved single-tablet regimen B/F/TAF. We report Week 96 results from an ongoing phase 3 study comparing B/F/TAF to coformulated dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) in treatment-naïve adults living with HIV-1. Primary outcome at W48 demonstrated noninferior virologic responses, similar bone and renal profiles, and no viral resistance.

Methods
We randomized 1:1 HLA-B*5701-negative adults, without HBV and with estimated glomerular filtration rate (eGFR) ≥50 mL/minute to receive blinded B/F/TAF (50/200/25 mg) or DTG/ABC/3TC (50/600/300 mg) with matching placebos QD. Primary endpoint was proportion with HIV-1 RNA &lt;50 copies/mL at W48 (FDA snapshot), with secondary analyses at W96. Noninferiority was assessed with 95% confidence intervals (CI) (12% margin). Other secondary endpoints were safety (adverse events [AEs], laboratory abnormalities) and predefined analyses of bone mineral density (BMD) and measures of renal function (eGFR, proteinuria).

Results
A total of 629 adults were randomized/treated (314 B/F/TAF, 315 DTG/ABC/3TC). At W96, B/F/TAF was noninferior to DTG/ABC/3TC: 87.9% vs. 89.8%, respectively, achieved HIV-1 RNA &lt;50 copies/mL (difference −1.9%; 95%CI −6.9% to 3.1%, P = 0.45). In per-protocol analysis, 99.6% on B/F/TAF vs. 98.9% on DTG/ABC/3TC achieved HIV-1 RNA &lt;50 copies/mL (P = 0.33). Most common AEs overall were nausea (11% B/F/TAF, 24% DTG/ABC/3TC, P &lt; 0.001), diarrhea (15%, 16%), and headache (13%, 16%). Through W96, no participant had emergent resistance to study drugs. No participant discontinued B/F/TAF due to AEs; five (2%) discontinued DTG/ABC/3TC due to AEs (one after W48). Treatment-related AEs occurred in 28% B/F/TAF vs. 40% DTG/ABC/3TC (P = 0.002); most common was nausea (6%, 17%. P &lt; 0.001). At W96, mean percentage changes in spine and hip BMD were small and similar between groups (table); median change in eGFR was significantly less with B/F/TAF, while median % changes in proteinuria were similar.

Conclusion
At W96, B/F/TAF was virologically noninferior to DTG/ABC/3TC, with no viral resistance or safety-related discontinuations. B/F/TAF was well tolerated with less nausea than DTG/ABC/3TC and similar bone and renal safety.

Disclosures
D. A. Wohl, Gilead: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Y. Yazdanpanah, AbbVie: Consultant, Consulting fee. Bristol-Myers Squibb: Consultant, Consulting fee. Gilead: Consultant, Consulting fee. MSD: Consultant, Consulting fee. Pfizer: Consultant, Consulting fee. Johnson & Johnson: Consultant, Consulting fee. ViiV Healthcare: Consultant, Consulting fee. A. Baumgarten, AbbVie: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. BMS: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Gilead: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Janssen-Cilag: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. MSD: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. ViiV: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. A. Clarke, GSK: Scientific Advisor, Consulting fee. Gilead: Conference attendence, Scientific Advisor and Speaker’s Bureau, Conference attendance support, Consulting fee and Speaker honorarium. BMS: Conference attendence, Conference attendance support. Janssen: Conference attendence, Conference attendance support. M. Thompson, Bristol Myers Squibb: Research Contractor, Research support. ViiV Healthcare: Research Contractor, Research support. C. Brinson, Gilead: Investigator, Scientific Advisor and Speaker’s Bureau, Research support and Speaker honorarium. Theratech: Investigator, Research support. BMS: Investigator, Research support. SlieaGen: Investigator, Research support. GSK ViiV: Consultant, Investigator and Scientific Advisor, Consulting fee, Research support and Speaker honorarium. Daiichi Sankyo: Sub Investigator, Research support. Novo Nordisk: Investigator, Research support. Sanofi: Investigator, Research support. Watson: Investigator, Research support. Salix: Investigator, Research support. Janssen: Investigator, Research support. Roche: Investigator, Research support. Colucid: Investigator, Research support. Eisai: Investigator, Research support. Shionogi: Investigator, Research support. Elcelyx: Investigator, Research support. Sangamo: Sub Investigator, Research support. D. Hagins, GlaxoSmithKline: Scientific Advisor and Speaker’s Bureau, Honoraria and Speaker honorarium. ViiV Healthcare: Scientific Advisor and Speaker’s Bureau, Honoraria and Speaker honorarium. Gilead: Scientific Advisor, Honoraria and Speaker honorarium. Bristol-Myers Squibb: Scientific Advisor and Speaker’s Bureau, Honoraria and Speaker honorarium. M. Ramgopal, Gilead: Grant Investigator, Research grant. A. Antinori, AbbVie: Consultant, Consulting fee. BMS: Consultant and Grant Investigator, Consulting fee and Research grant. Gilead: Consultant and Grant Investigator, Consulting fee and Research grant. Janssen-Cilag: Consultant and Grant Investigator, Consulting fee and Research grant. Merck: Consultant, Consulting fee. ViiV Healthcare: Consultant and Grant Investigator, Consulting fee and Research grant. X. Wei, Gilead: Shareholder, Salary and Stock. K. White, Gilead: Employee and Shareholder, Salary and Stock. S. Collins, Gilead: Employee and Shareholder, Salary and Stock. A. Cheng, Gilead: Employee and Shareholder, Salary and Stock. E. Quirk, Gilead: Employee and Shareholder, Salary and Stock. H. Martin, Gilead: Employee and Shareholder, Salary and Stock.