
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.

D. A. Wohl,
Gilead:
Grant Investigator
and
Scientific Advisor
,
Consulting fee
and
Research grant
.
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 .
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