TUPE043 - Poster Exhibition
Analysis of efficacy by baseline viral load: phase 3 study comparing elvitegravir/cobicistat/emtricitabine/tenofovir DF (quad) versus ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF in treatment-naïve HIV-1-positive subjects: week 48 res
E. DeJesus1, J. Rockstroh2, K. Henry3, J.-M. Molina4, J. Gathe5, S. Ramanathan6, X. Wei6, K. Yale6, J. Szwarcberg6, K. White6, A. Cheng6, B. Kearney6
1Orlando Immunology Center, Orlando, United States, 2University of Bonn, Bonn, Germany, 3Hennepin County Medical Center, Mineapolis, United States, 4Saint Louis Hospital, Paris, France, 5Therapeutic Concepts P.A., Houston, United States, 6Gilead Sciences, Foster City, United States
disoproxil fumarate(TDF)(“Quad”) is the first once-daily integrase inhibitor-based
single tablet regimen in clinical development.
Methods: Subjects with HIV RNA (VL) ≥ 5000 c/mL, CLCr
>70 mL/min, no prior HIV therapy, and no resistance to ATV, FTC, or
TDF were randomized to receive Quad or ATV/r+FTC/TDF in a multinational, blinded,
active-controlled study. Primary endpoint was VL<
50 copies/mL at Week 48 by snapshot algorithm; noninferiority margin was
Results: 708 subjects were randomized
and treated: 90% male, 26% non-white, median VL 4.87 log10copies mL,
41% with VL ≥100,000 c/mL. Quad was noninferior to ATV/r+FTC/TDF in achieving VL<50
c/mL at Wk48 (90% vs 87%) (difference 3.0%, 95% CI: -1.9 to 7.8). Virologic response rates were high in both
Quad and ATV/r+FTC/TDF group among subjects with high baseline VL >100,000
c/mL) (85% vs. 82%) and those with low baseline VL (≤100,000 c/mL) (93% vs. 90%).
Efficacy of Quad was consistent across all subgroups (Figure). Overall virologic
failure was infrequent (5% in both groups). Mean CD4 increases were similar
(207 vs. 211 cells/µL). Discontinuation rates for adverse events (AE) were
similar (4% vs. 5%). The rate of Grade 3 or 4 hyperbilirubinemia was lower in
Quad (1% vs. 58%). Median CLCr change from baseline was -12.7 in
Quad and -9.5 mL/min in ATV/r+FTC/TDF. Median triglyceride increases were 8 in
Quad and 23 mg/dL in ATV/r+FTC/TDF (p=0.006). PK-PD
analyses showed ≥ 90% efficacy across all quartiles or octiles for EVG Ctrough.
Median spine BMD changes in Quad
vs. ATV/r+FTC/TDF were -2.45% and -3.46%; for
hip, changes were -2.87% and -3.59% (p>0.05 for both).
Conclusions: Quad demonstrated
noninferior efficacy and was well-tolerated at 48 weeks. The efficacy of Quad
was robust in patients regardless of baseline VL. These data support the use of Quad as a
potential new STR option for initial HIV treatment irrespective of baseline VL.
[Efficacy in subgroups (HIV-1 RNA < 50 copies/mL)]
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