A phase 3 randomized controlled clinical trial of bictegravir in a fixed dose combination, B/F/TAF, vs ABC/DTG/3TC in treatment-naive adults at Week 48
Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar E, Wohl D, Rockstroh J, Wei X, White K, Martin H, Quirk E, and Cheng A. A phase 3 randomized controlled clinical trial of bictegravir in a fixed dose combination, B/F/TAF, vs ABC/DTG/3TC in treatment-naive adults at Week 48. J Int AIDS Soc 2017; 20(Suppl 5):103-104.
J Int AIDS Soc
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-naive, HLA-B*5701-negative, HBV-uninfected adults with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min were randomized 1:1 to receive blinded treat- ment with fixed-dose combination B/F/TAF (50/200/25mg) or ABC/ DTG/3TC (600/50/300mg) with matching placebos once daily. The primary endpoint was proportion of participants with HIV-1 RNA (VL)/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/mL. Median baseline charac- teristics: age 32 yrs, CD4 count 444 cells/μL and VL 4.47 log10 c/ mL. At W48, B/F/TAF was non-inferior to ABC/DTG/3TC, with 92.4% on B/F/TAF and 93.0% on ABC/DTG/3TC achieving HIV-1 RNA/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 com- mon AEs were diarrhoea (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 percentage changes from baseline in BMD were − 0.83% versus − 0.60% ( p = 0.39) (lumbar spine) and − 0.78% versus − 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-naive 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.