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Simplification with Fixed-dose Tenofovir/Emtricitabine or Abacavir/Lamivudine in Adults with Suppressed HIV Replication: The STEAL Study, a Randomized, Open-label, 96-Week, Non-inferiority Trial
D Cooper1, M Bloch2, A Humphries1, J Amin1, D Baker3, S Emery1, Andrew Carr*4, and for the STEAL Study Investigators
1Natl Ctr in HIV Epi and Clinical Res, Univ of New South Wales, Sydney, Australia; 2Holdsworth House Gen Practice, Sydney, Australia; 3East Sydney Doctors, Australia; and 4St Vincent`s Hosp, Sydney, Australia
Background: There are 2 once-daily,
dual-nucleoside, fixed-dose-combination (FDC) tablets that are used for adult
HIV-1 infection: tenofovir (TDF; 300 mg) + emtricitabine (FTC; 200 mg); and
abacavir (ABC; 600 mg) + lamivudine (3TC; 300 mg). Which FDC is more effective
and safe is uncertain.
Methods: We compared TDF+FTC- and ABC+3TC-based
therapy over 96 weeks when either FDC was substituted for current NRTI in HLA-B*5701–
adults with plasma HIV viral load <50 copies/mL. The primary endpoint was virological
failure, defined by repeat viral load >400 copies/mL plasma by
intention-to-treat, missing=failure (ITTM=F) analysis. Secondary endpoints (ITT)
included death, AIDS, serious non-AIDS events (see table), metabolic parameters
and body composition (bone/soft-tissue; ITT-LOCF). We used exact statistics for
differences in proportions, t tests to compare means, and Cox regression
for hazard ratios for ABC+3TC/TDF+FTC (HR 95%CI).
Results: From January to August 2006, we randomized 360
patients. Key baseline characteristics of the 357 treated participants were: male
98%, mean age 45.1 years, prior NRTI therapy 5.8 years, current TDF 30%, current
ABC 20%, current PI 24%, mean CD4 count 612 cells/mm3, eGFR 98 mL/min/1.73
m2, limb fat 5.5 kg, and hip t score –0.49. Groups were well balanced,
except smoking was more prevalent with ABC+3TC (40%) than with TDF+FTC (29%); 1.7%
were lost to follow-up with no between-group difference. No patient developed
AIDS or renal failure. TDF+FTC was associated with more bone loss. There was no
significant between-group, week-96 difference for limb fat, eGFR, CD4 count,
insulin sensitivity, total:HDL cholesterol ratio, or lactate.
|
Parameter (to week 96)
|
TDF+FTC
n = 178
|
ABC+3TC
n = 179
|
|
p
|
|
|
n (%)
|
Difference (95%CI)
|
|
|
Virological failure
|
7 (3.9%)
|
10 (5.6%)
|
1.7% (–2.8%, 6.1%)
|
0.62
|
|
|
n (Rate / 100 patient-years)
|
HR (95%CI)
|
|
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Serious non-AIDS
|
5 (1.5)
|
15 (4.8)
|
0.30 (0.11, 0.84)
|
0.022
|
|
Ischemic cardiovascular disease
|
1
|
7*
|
0.15 (0.02, 1.15)
|
0.067
|
|
Cancer (not skin SCC / BCC)
|
2
|
5
|
|
|
|
Major fracture
|
2
|
2
|
|
|
|
Cirrhosis
|
0
|
1
|
|
|
|
Death (all from cancer)
|
1
|
3
|
|
|
|
TDF+FTC / ABC+3TC cessation
|
17 (14.9)
|
21 (18.8)
|
0.80 (0.42, 1.51)
|
0.49
|
|
New lipid-lowering therapy
|
12 (3.7)
|
29 (9.6)
|
0.39 (0.20, 0.76)
|
0.006
|
|
|
Mean change
|
Difference (95%CI)
|
|
|
Hip T-score
|
–0.07
|
0.09
|
0.16 (0.08, 0.23)
|
<0.0001
|
* 3 myocardial infarctions; 2 leg arterial disease; 1 stroke,
1 coronary artery by-pass
Conclusions: In this population, TDF+FTC and ABC+3TC
had similar virological efficacy and protection against AIDS. ABC+3TC was
associated with more serious non-AIDS events.
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