TUPE028 - Poster Exhibition
Analysis of efficacy by baseline HIV RNA: week 48 results from a phase 3 study of elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) compared to efavirenz/emtricitabine/tenofovir DF in treatment-naïve HIV-1-positive subjects
P. Sax1, E. De Jesus2, A. Mills3, A. Zolopa4, C. Cohen5, D. Wohl6, J. Gallant7, H. Liu8, L. Zhong8, K. Yale8, K. White8, B. Kearney8, J. Szwarcberg8, E. Quirk8, A. Cheng8, GS-US-236-0102 Study Group
1Brigham & Women's Hospital, Boston, United States, 2Orlando Immunology Center, Orlando, United States, 3Anthony Mills MD, Inc, Los Angeles, United States, 4Stanford University, Palo Alto, United States, 5Community Research Initiative of New England, Boston, United States, 6University of North Carolina, Chapel Hill, United States, 7Johns Hopkins School of Medicine, Baltimore, United States, 8Gilead Sciences, Foster City, United States
Background: Elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate.(TDF) (“Quad”) is the first once-daily integrase inhibitor-based single tablet regimen in clinical development.
Methods: North American, treatment-naïve subjects with HIV RNA ≥ 5,000 copies/mL (c/mL), CLCr > 70 mL/min and sensitivity to EFV, FTC, and TDF who gave informed consent were randomized 1:1 to Quad or EFV/FTC/TDF QD. The primary endpoint was the proportion with HIV RNA < 50 c/mL at Week 48 (snapshot algorithm, -12% noninferiority margin).
Results: 700 subjects (89% male, 37% non-white, median baseline HIV RNA of 4.76 log10 c/mL, 33% with VL >100,000 c/mL) were treated. Virologic response to Quad (88%) was noninferior to EFV/FTC/TDF (84%) at Week 48 (snapshot algorithm, difference +3.6%, 95% CI -1.6%, +8.8%). Among subjects with high (>100,000 c/mL) and low (< 100,000 c/mL) baseline HIV RNA, response rates were similar for Quad (84% and 90%, respectively) and EFV/FTC/TDF (82% and 85%, respectively). Virologic failure rates at Week 48 were 7% in both arms. At Week 48, mean CD4 cell increase was 239 cells/µL in Quad and 206 cells/µL in EFV/FTC/TDF (p=0.009). Drug discontinuation rates for adverse events were similar (Quad 4%, EFV/FTC/TDF 5%). There was no difference in the rates of Grade 3 and 4 AEs. Median CLCr decreases were larger with Quad than EFV/FTC/TDF (-14.3 vs. -3.0 mL/min by Week 48, p < 0.001). Total cholesterol, HDL and LDL increases at Week 48 were significantly lower for Quad than EFV/FTC/TDF (p< or = 0.001 for all).
|Age (years), mean||38||38|
|Black or African heritage (%)||31%||26%|
|Asymptomatic HIV Infection (%)||83%||84%|
|HBV -- HCV antibody positive (%)||1% - 5%||3% - 4%|
|HIV-1 RNA (log10 c/mL), median||4.75||4.78|
|HIV-1 RNA >100,000 c/mL (%)||34%||33%|
|CD4 count (cells/mm3), mean||391||382|
[Percent Difference in Week 48 Response by Subgroup]
Conclusions: In this first Phase 3 study of 2 single tablet regimens, Quad demonstrated noninferior efficacy to EFV/FTC/TDF and was well tolerated at 48 weeks. The efficacy of Quad was robust in patients regardless of baseline HIV RNA. These data support the use of Quad as a potential new single tablet regimen option for initial HIV treatment irrespective of baseline viral load.
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