744 
Assessment of Renal Findings of Abacavir/Lamivudine Compared with Tenofovir/Emtricitabine in Combination with Once-daily Lopinavir/Ritonavir over 96 Weeks in the HEAT Study
Derek Fine*1, K Smith2, P Patel3, N Bellos4, L Sloan5, P Lackey6, P Kumar7, D Sutherland-Phillips3, L Yau3, and M Shaefer3
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Rush Univ Med Ctr, Chicago, IL, US; 3GlaxoSmithKline, Research Triangle Park, NC, US; 4Southwest Infectious Disease Assoc, Dallas, TX, US; 5North Texas Infectious Disease Consultants, Dallas, US; 6ID Consultants, Charlotte, NC, US; and 7Georgetown Univ Sch of Med, Washington, DC, US
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. Detailed comparison of the renal effects of
these regimens has not been performed.
Methods: ART-naïve subjects with plasma HIV-1 RNA (viral
load) ³1000 copies/mL, and any CD4+
count were randomized to receive abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitibine
(TDF/FTC) with open-label lopinavir/ritonavir (LPV/r) once daily in this double-blind,
placebo-matched, multi-center, 96-week study. The primary objective at 96 weeks
was to evaluate safety and tolerability. Detailed assessment of renal
parameters was carried out as part of safety assessment. Renal data were
collected through 96 weeks or the last sample date while subjects were still on
randomized treatment.
Results: We randomized 688 subjects who were: median
age 38 years, 18% female, 15% hypertensive, 3% diabetic, and 2% with renal or
urinary disorders at baseline; 5 subjects developed proximal tubule renal
dysfunction in the TDF/FTC arm according to predefined criteria. At the last
study visit on randomized treatment, small increases in the estimated glomerular
filtration rate (eGFR) and creatinine clearance (eCrCl) were observed in both
treatment arms. Progression to a more advanced CKD stage occurred in 31 (10%)
subjects in the ABC/3TC arm and 49 (15%) subjects in the TDF/FTC arm at the
last visit on study drug; 4 in the ABC/3TC arm and 11 in the TDF/FTC arm progressed
to stage 3 CKD (eGFR <60 mL/min/1.73m2).
|
|
ABC/3TC
n = 343
|
TDF/FTC
n = 345
|
|
Mean (SD)
|
Baseline
|
Last observed
|
Last observed change from baseline
|
Baseline
|
Last observation
|
Last observed change from baseline
|
|
Phosphorus
(mg/dL)
|
3.63 (0.694)
|
3.20 (0.646)
|
–0.43
(0.820)
|
3.71 (0.732)
|
3.22
(0.673)
|
-0.49
(0.832)
|
|
Creatinine (mg/dL)
|
1.05 (0.219)
|
1.01 (0.211)
|
–0.04
(0.18)
|
1.04 (0.217)
|
1.05
(0.236)
|
0.00
(0.200)
|
|
MDRD (eGFR)
(mL/min/1.732)
|
90.0 (19.2)
|
93.7 (19.2)
|
3.4
(16.7)
|
90.4 (20.5)
|
90.6
(21.7)
|
0.7
(18.7)
|
|
C-G CrCl
(mL/min)
|
105.4 (26.6)
|
113.4 (29.6)
|
7.8
(19.7)
|
103.3 (26.1)
|
108.2
(32.4)
|
5.0
(19.4)
|
|
Urine glucose ³15*
mg/dL
|
5/224 (2%)
|
10/247 (4%)
|
NA
|
10/235 (4%)
|
11/261 (4%)
|
NA
|
* Excluded subjects: known diabetes, fasting glucose
>126, any glucose >140 at any time-point
Conclusions: These results show that improvement in
kidney function, as measured by eGFR and eCrCl, was slightly greater, though
small in absolute terms, with ABC/3TC compared to TDF/FTC when combined with
once-daily LPV/r through 96 weeks. In addition, fewer subjects in ABC/3TC group
progressed to stage 3 CKD. Proximal tubule renal dysfunction, though not
common, was seen only in those on TDF/FTC.
|
