|
Similarity in efficacy and safety of abacavir/lamivudine (ABC/3TC) compared to tenofovir/emtricitabine (TDF/FTC) in combination with QD lopinavir/ritonavir (LPV/r) over 96 weeks in the HEAT Study
K.Y. Smith1, D.M. Fine2, P. Patel3, N.C. Bellos4, L. Sloan5, P. Lackey6, P.N. Kumar7, D.H. Sutherland-Phillips3, C. Vavro3, L. Yau3, M.S. Shaefer3
1Rush University Medical Center, Chicago, United States, 2Johns Hopkins University School of Medicine, Baltimore, United States, 3GlaxoSmithKline, Research Triangle Park, United States, 4Southwest Infectious Disease Associates, Dallas, United States, 5North Texas Infectious Disease Consultants, Dallas, United States, 6ID Consultants, Charlotte, United States, 7Georgetown University, Washington, United States
Background: HEAT is the first large, prospective, long-term, head-to-head trial to evaluate the efficacy and safety of these dual NRTI backbones with a boosted PI as part of recommended first-line treatments in HIV-1 infected subjects.
Methods: ART-naive subjects with plasma HIV-1 RNA (VL) ³1000 copies/mL (c/mL), [stratified < or ³100,000 c/mL], and any CD4+ count were randomized to receive ABC/3TC or TDF/FTC with open-label LPV/r QD in this double-blind, placebo-matched, multi-center, 96-week study. Virologic failure (VF) was defined as failure to achieve VL<200 c/mL by Week 24 or confirmed rebound to ³ 200 c/mL. The primary objective at 96 weeks was to evaluate safety and tolerability.
Results: 688 were randomized with mean age of 38 years, 18% female, 49% non-white, baseline median VL 4.87 log10c/mL and CD4+ 202 cells/cmm. Virologic failure occurred in 14% for both groups.
Week 96 Results
ITT-E, M=F, Switch Included Analysis* | ABC/3TC + LPV/r
n=343 | TDF/FTC + LPV/r
n=345 | 95% CI of Difference | p-value | VL<50 c/mL*,
BL VL<100,000 c/mL
BL VL ³100,000 c/mL | 60%
63%
56% | 58%
58%
58% | (-5.41,9.32)
---
--- | 0.603
---
--- | | VL<50 c/mL, TLOVR | 52% | 51% | (-6.33,8.63) | 0.763 | | Median CD4+ (D from BL), cells/cmm | 466 (+250) | 445 (+247) | | | Prematurely Withdrawn due to AEs | 20 (18%) | 21 (17%) | | | Drug-related Grade 3-4 AEs | 50 (15%) | 52 (15%) | | | Drug-related Serious AEs excluding ABC HSR | 4 (1%) | 6 (2%) | | | Suspected ABC HSR | 14 (4%) | 3 (<1%) | | | Proximal Renal Tubule Dysfunction | 0 | 6 (2%) | |
Conclusions: These results demonstrate ABC/3TC is virologically noninferior to TDF/FTC when combined with once-daily LPV/r through 96 weeks. Response rates by low and high baseline VL strata were similar in both arms. VF rates and treatment-limiting adverse events were also comparable between arms.
|