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
Session: Oral Abstract Session: Late Breaker Oral Abstracts: HIV and Antibiotic Trials
Thursday, October 4, 2018: 11:00 AM
Room: S 151-153

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 (W) 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/min 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 <50 c/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: 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 <50 c/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 <50c/mL (p=0.33). Most common AEs overall were nausea (11% B/F/TAF, 24% DTG/ABC/3TC, p<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; 5 (2%) discontinued DTG/ABC/3TC due to AEs (1 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<0.001). At W96, mean % 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.

David A. Wohl, MD1, Yazdan Yazdanpanah, MD2, Axel Baumgarten, MD3, Amanda Clarke, M.D.4, Melanie Thompson, MD5, Cynthia Brinson, M.D.6, Debbie Hagins, MD7, Moti Ramgopal, MD, FACP, FIDSA8, Andrea Antinori, MD9, Xuelian Wei, PhD10, Kirsten White, PhD10, Sean Collins, MD10, Andrew Cheng, MD PhD10, Erin Quirk, MD10 and Hal Martin, MD, MPH10, (1)Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, (2)Hôpital Bichat Claude Bernard, Paris, France, (3)Zentrum für Infektiologie Berlin Prenzlauer Berg (ZIBP), Berlin, Germany, (4)HIV/Gum and Clinical Trials, Brighton & Sussex University Hospitals NHS Trust, Brighton, United Kingdom, (5)AIDS Research Consortium of Atlanta, Atlanta, GA, (6)Central Texas Clinical Research, Austin, TX, (7)Chatham County Health Department, Savannah, GA, (8)Midway Immunology and Research Center, Fort Pierce, FL, (9)National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Roma, Italy, (10)Gilead Sciences, Foster City, CA

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 .

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.