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Efficacy and Safety of Abacavir/Lamivudine Compared to Tenofovir/Emtricitabine in Combination with Once-daily Lopinavir/Ritonavir through 48 Weeks in the HEAT Study
Kimberly Smith*1, D Fine2, P Patel3, N Bellos4, L Sloan5, P Lackey6, D Sutherland-Phillips3, C Vavro3, Q Liao3, and M Shaefer3
1Rush Univ Med Ctr, Chicago, IL, US; 2Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 3GlaxoSmithKline, Research Triangle Park, NC, US; 4Southwest Infectious Disease Assoc, Dallas, TX, US; 5North Texas Infectious Disease Consultants, Dallas, US; and 6ID Consultants, Charlotte, NC, US
Background: Limited direct comparative data exist
between the recommended dual NRTI fixed-dose combinations, abacavir/lamivudine
(ABC/3TC) and tenofovir/emtricitabine (TDF/FTC). HEAT is the first 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: Randomized (1:1), double-blind, placebo-matched,
multi-center, 96-week, non-inferiority study design. HIV-1-infected, ARV-naïve subjects
had a plasma HIV-1 RNA (viral load) ≥1000 copies/mL, (stratified < or
≥100,000 copies/mL), and any CD4+ count. Subjects received
either blinded ABC/3TC or TDF/FTC with open-label lopinavir/ritonavire (LPV/r) soft
gel capsule once daily. Protocol-defined virologic failure was defined as failure
to achieve viral load <200 copies/mL by week 24 or confirmed rebound to ≥200
copies/mL. Primary efficacy endpoint was the proportion of subjects with viral
load <50 copies/mL at week 48 (intent to treat, M = F, switch included
analysis). For the difference in responses between arms, 95%CI was calculated
to show non-inferiority using a 12% margin. Primary safety endpoint will be at week
96. Within-class switches were allowed for toxicity. HLA-B*5701
screening was not performed.
Results: We randomized 688 subjects whose mean age was
38 years; 18% were female.
|
|
ABC/3TC + LPV/r
n = 343
|
TDF/FTC + LPV/r
n = 345
|
|
|
Baseline
Characteristics
|
|
Race
White
African
American
Other
|
51%
36%
13%
|
49%
36%
15%
|
|
|
Median HIV-1 RNA (log10) copies/mL
≥100,000 copies/mL
|
4.90
45%
|
4.84
41%
|
|
Median CD4+, cells/mm3
|
214
|
193
|
|
Week 48 Results
|
|
|
95%CI of Difference
|
p value
|
|
HIV-1 RNA <50
ITT-E,
M=F, Switch Included
TLOVR
Observed
|
68%
63%
84%
|
67%
61%
87%
|
(–6.63 to 7.40)
(–5.75 to 8.78)
(–8.44 to 3.34)
|
0.913
0.683
0.399
|
|
HIV-1
RNA <400
ITT-E,
M=F, Switch Included
Observed
|
75%
94%
|
71%
92%
|
(–2.71 to 10.56)
(–2.69 to 5.89)
|
0.246
0.467
|
|
Median
CD4+ (ΔBL), cells/mm3
|
429
(+201)
|
370 (+173)
|
|
|
Protocol-defined VF
|
12%
|
13%
|
|
Prematurely Withdrawn, n (%)
|
68 (20%)
|
83 (24%)
|
|
Withdrawn
due to Adverse Events
|
13
(19%)
|
20
(24%)
|
|
Drug-related
Grade 2-4 Adverse Events
|
154
(45%)
|
152
(44%)
|
|
Suspected
ABC HSR Toxicity Switches
|
14
(4%)
|
3
(1%)
|
|
Proximal
Renal Tubular Dysfunction
|
0
|
3
(1%)
|
Conclusions: ABC/3TC was noninferior to TDF/FTC when
combined with once-daily LPV/r. Median CD4+ increase was greater in
the ABC/3TC arm at week 48. Rates of drug-related grade-2 to -4 adverse events
were comparable between arms. Both once-daily treatment regimens proved
efficacious in this ART-naïve population through 48 weeks.
|
