Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD

Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072 ; Wohl DA Lancet HIV 2019 ; 6:e355-63

Type of ARV Trial
Head-to-head comparative trials for first line ART since 2006
» INSTI vs INSTI
» BIC/FTC/TAF vs DTG/ABC/3TC
Drugs
BIC/FTC/TAF, DTG, FTC/TAF, ABC/3TC, ABC, 3TC

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  • Summary of week 96 results
    • Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W96 by snapshot algorithm
      • 87.9% of patients on BIC/F/TAF and 89.8% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL
    • No treatment emergent resistance
    • BIC/F/TAF was well tolerated, with no adverse events leading to discontinuation
      • Nausea was reported significantly more frequently in patients treated with DTG/ABC/3TC (p < 0.001)
      • Gastrointestinal, neuropsychiatric, and sleep-related symptoms were reported more frequently in patients treated with DTG/ABC/3TC
      • Decrease in eGFR was significantly higher on DTG/ABC/3TC
      • Increase in total-cholesterol and LDL-cholesterol was significantly higher on BIC/F/TAF, but the proportion of participants initiating lipid-lowering agents was not different between arms

Design


* Randomisation was stratified by HIV RNA (< 100 000 c/mL, 100 000-4000 000 c/mL or > 100 000 c/mL), CD4 (< 50/mm3, 50-199/mm3 or ≥ 200/mm3) at screening and geographic region (USA vs non-USA)
BIC/F/TAF : 50/200/25 mg, as STR

Objective

  • Non inferiority of BIC/F/TAF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 2-sided 95.002% CI for the difference= -12%, 95% power)

Baseline characteristics and patient disposition

Virologic outcome at week 48

  • HIV RNA < 50 c/mL (per-protocol)
    • BIC/F/TAF: 99.3%
    • DTG/ABC/3TC: 98.6%
  • Met criteria for resistance testing (HIV RNA ≥ 200 c/mL)
    • BIC/F/TAF: 1 vs DTG/ABC/3TC: 4
    • No resistance emergence
  • Mean CD4 increase at W48
    • BIC/F/TAF: + 233/mm3
    • DTG/ABC/3TC: + 229/mm3

HIV RNA < 50 c/mL at W48 according to baseline CD4 and HIV RNA, ITT-E snapshot

Adverse events at W48


* Nausea, rash ; thrombocytopenia ; chronic pancreatitis, steatorrhea ; depression
** p < 0.001

Renal parameters, bone mineral density and lipid changes at W48

  • None of the differences between groups were significant
  • No discontinuations due to renal adverse events and no proximal tubulopathy in either arm

Steady-state pharmacokinetic parameters of BIC/F/TAF (N = 17)

* BIC mean Ctau about 14 times higher than the protein adjusted effective concentration (162 ng/mL) against wild type HIV-1 virus.

Summary of week 48 results

  • Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W48 by snapshot algorithm
    • 92.4% of patients on BIC/F/TAF and 93.0% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL
    • Sensitivity analyses confirmed non inferiority
  • No treatment emergent resistance
  • BIC/F/TAF was well tolerated, with no adverse events leading to discontinuation
    • Nausea was reported significantly more frequently in patients treated with DTG/ABC/3TC (p < 0.001)
    • Gastrointestinal, neuropsychiatric, and sleep-related symptoms were reported more frequently in patients treated with DTG/ABC/3TC
    • Changes from baseline in bone mineral density, lipid parameters and renal markers were comparable between treatment arms

Virologic outcome at week 96, ITT snapshot

Secondary endpoints at week 96

Adverse events at W96

  • Discontinuation for adverse event

  • Adverse events all grades (%)

  • Laboratory parameters (W96)

  • Bone DXA: mean % change in BMD between D0 and W96

Mean changes in fasting lipids at W96, mg/dL