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

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.