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Background: In a phase 2 study, bictegravir (BIC, B), a novel, potent integrase strand transfer inhibitor (INSTI) with a high barrier to resistance, was directly compared with dolutegravir (DTG), each given with the recommended N(t)RTI combination of emtricitabine and tenofovir alafenamide (F/TAF) in treatment-naïve, HIV-infected adults. Both treatments demonstrated high efficacy and were well tolerated through Week (W) 48. We now report results from a phase 3 study of this comparison of BIC and DTG, each with F/TAF, utilizing a single-pill coformulation of B/F/TAF.
Methods: Treatment-naïve, HIV-infected adults with estimated glomerular filtration rate (eGFR)
≥30 mL/min were randomized 1:1 to receive blinded treatment with fixed dose combination B/F/TAF (50/200/25 mg) or DTG (50 mg) + F/TAF (200/25 mg) with matching placebos once daily through W48. Chronic hepatitis B and/or C infection was allowed. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL (c/mL) at W48 (FDA snapshot). Noninferiority was assessed through 95.002% confidence intervals (CI) using a margin of 12%. Secondary endpoints were safety measures (adverse events [AEs] and laboratory results).
Results: 645 participants were randomized and treated (320 B/F/TAF, 325 DTG + F/TAF): 12% women, 31% Black, 19% viral load (VL) >100,000 c/mL, 12% CD4 < 200 cells/µL, median age 34 yrs, CD4 count 440 cells/µL, and VL 4.44 log10 c/mL. At W48, B/F/TAF was noninferior to DTG + F/TAF, with 89.4% on B/F/TAF and 92.9% on DTG + F/TAF achieving HIV-1 RNA < 50 c/mL (difference -3.5%; 95.002%CI -7.9% to 1.0%, p=0.12). At W48, proportion of participants with HIV-1 RNA ≥50 c/mL was < 1% in each arm. No study subject in either treatment arm developed resistance to any of the study drugs. The most common AEs were headache (13% B/F/TAF, 12% DTG + F/TAF) and diarrhea (12% for both). Few participants (5 [2%], 1 [< 1%]) had AEs leading to premature study discontinuation. Lipid changes were not significantly different between study arms. No renal discontinuations and no cases of proximal renal tubulopathy were reported.
Conclusions: After 48 weeks, B/F/TAF achieved virologic suppression in 89.4% of treatment- naïve adults and was noninferior to DTG + F/TAF. B/F/TAF was safe and well tolerated.