Background: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line antiretroviral therapy in combination with 2 nucleoside reverse transcriptase inhibitors. Bictegravir (B), a novel, potent INSTI with a high in vitro barrier to resistance and low potential for drug interactions, has been coformulated with emtricitabine (F) and tenofovir alafenamide (TAF) as a fixed-dose combination (B/F/TAF). We report results from a blinded phase 3 study comparing B/F/TAF to coformulated abacavir, dolutegravir, and lamivudine (ABC/DTG/3TC).
Methods: HIV-infected, treatment-naïve, HLA-B*5701-negative, HBV-uninfected adults with estimated glomerular filtration rate (eGFR) ≥50 mL/min were randomized 1:1 to receive blinded treatment with fixed-dose combination B/F/TAF (50/200/25 mg) or ABC/DTG/3TC (600/50/300 mg) with matching placebos once daily. The primary endpoint was proportion of participants with HIV-1 RNA (VL) < 50 c/mL at W48 (FDA snapshot). Noninferiority was assessed through 95.002% confidence intervals (CI) (12% margin). Secondary endpoints were safety (adverse events [AEs] and laboratory abnormalities) and pre-defined analyses of changes from baseline in bone mineral density (BMD) and measures of renal function, including eGFR and proteinuria.
Results: 629 participants were randomized and treated (314 B/F/TAF, 315 ABC/DTG/3TC): 10%
women, 36% Black, 16% VL >100,000 c/mL, 11% CD4 < 200 cells/mL. Median baseline characteristics: age 32 yrs, CD4 count 444 cells/µL, and VL 4.47 log10 c/mL. At W48, B/F/TAF was noninferior to ABC/DTG/3TC, with 92.4% on B/F/TAF and 93.0% on ABC/DTG/3TC achieving HIV-1 RNA < 50 c/mL (difference -0.6%; 95.002%CI -4.8% to 3.6%, p=0.78). No resistance mutations emerged in either group. Comparing B/F/TAF to ABC/DTG/3TC throughout, the most common AEs were diarrhea (13%, 13%), headache (11%, 14%), and nausea (10%, 23%). Few participants (0 vs 4 [1%]) had any AEs leading to premature study drug discontinuation. At W48, mean % changes from baseline in BMD were -0.83% vs. -0.60% (p=0.39) [lumbar spine] and -0.78% vs. -1.02% (p=0.23) [total hip]. No differences between treatments were noted in changes from baseline for eGFR and proteinuria at W48.
Conclusions: At W48, B/F/TAF achieved virologic suppression in 92.4% of treatment-naïve adults and was noninferior to ABC/DTG/3TC, with no emergent resistance. B/F/TAF was safe and well tolerated with less nausea than ABC/DTG/3TC. Bone and renal safety profiles were similar between groups.