1. Comparison of NRTI combinations
ARV-trial.com
Comparison of NRTI combinations
ZDV/3TC vs TDF + FTC
Study 934
ABC/3TC vs TDF/FTC
HEAT Study
ACTG A5202 Study
ASSERT Study
FTC/TDF vs FTC/TAF
Studies GS-US and GS-US 1

2. HEAT Study: ABC/3TC vs TDF/FTC
ARV-trial.com
HEAT Study: ABC/3TC vs TDF/FTC
Design
Randomisation*
1 : 1
Double-blind
placebo-matched
W48
W96
N = 343
ABC/3TC + TDF/FTC placebo QD
LPV/r 800/200 mg
694 ARV-naïve patients
> 18 years
HIV RNA > 1,000 c/mL
Any CD4 cell count
No HLA-B*5701 screening
N = 345
TDF/FTC + ABC/3TC placebo QD
LPV/r 800/200 mg
*Randomisation was stratified on HIV RNA < 100,000 c/mL or > 100,000 c/mL
Objective
Non inferiority of the 2 fixed dose NRTI combinations at W48: % HIV RNA < 50 c/mL, ITT-exposed, missing = failure [ITT-E, M = F] (lower margin of the 95% CI for the difference = - 12%, 90% power)
Primary safety endpoint: incidence of adverse events at W96
HEAT
Smith KY. AIDS 2009;23: 2

3. HEAT Study: ABC/3TC vs TDF/FTC
ARV-trial.com
HEAT Study: ABC/3TC vs TDF/FTC
Patient disposition and baseline characteristics
Randomized
ABC/3TC N = 347
TDF/FTC N = 347
Treated eligible patients, N
343
345
Median age, years 38
Female
16%
20%
White/Black/Other
52% / 36% / 13%
51% / 36% / 13%
HIV RNA (log10 c/mL), median
4.9
4.8
HIV RNA > 100,000 c/mL
45%
41%
CD4 cell count (/mm3), median
214
193
CD4 < 200/mm3
47%
52%
CD4 < 50/mm3
18%
HBV positive/HCV positive
6% / 8%
3% / 7%
Discontinuation by W96
N = 109 (32%)
N = 124 (36%)
For virologic failure/adverse event, N
8 / 20
6 / 21
Lost to follow-up/subject decision/non compliance, N
45 / 13 / 10
52 / 23 / 11
Note: change of NRTI (to NRTI other than ABC or TDF) allowed if intolerance;
change of LPV/r QD to BID allowed if gastrointestinal intolerance, or to other PI if LPV/r-limiting intolerance.
LPV/r was administered as soft-gel capsules (6/d) to week 48 then as tablets (4/d)
HEAT
Smith KY. AIDS 2009;23: 3

4. HEAT Study: ABC/3TC vs TDF/FTC
ARV-trial.com
HEAT Study: ABC/3TC vs TDF/FTC
Proportion of patients with HIV RNA < 50 c/mL at week 48 %
ABC/3TC
TDF/FTC
100
Primary efficacy
endpoint 87 84 80 71 68 69 67 63 64 65 61 62 63 60 40 20
N =
343
345
343
345
343
345
188
205
155
140
ITT-E, M/D = F
TLOVR
ITT, M/D = F
Observed analysis,
ITT-E
ITT-E, M/D = F stratified by
baseline HIV RNA (c/mL)
95% CI for the difference = - 6.6; 7.4
<
>
Median CD4 increase at W96: 250/mm3 (ABC/3TC) vs 247/mm3 (TDF/FTC)
ITT-E, M = F: ITT-exposed, missing/discontinuation = failure
HEAT
Smith KY. AIDS 2009;23: 4

5. HEAT Study: ABC/3TC vs TDF/FTC
ARV-trial.com
HEAT Study: ABC/3TC vs TDF/FTC
Safety and tolerability (median exposure = 96 weeks)
ABC/3TC N = 343
TDF/FTC N = 345
Grade 2-4 drug related adverse events
Any
50%
46%
Diarrhoea
19%
Nausea 8% 6%
Increased triglycerides
Increased cholesterol 7% 4%
Decreased Glomerular Filtration Rate 5%
Suspected Hypersensitivity Reaction to ABC 3%
<1%
Any drug-related serious adverse events
N = 18 * (5%)
N = 10 ** (3%)
Discontinuation for adverse event
* Including suspected ABC HSR (N = 14), immune reconstitution syndrome (N = 2), hepatotoxicity (N = 1)
** Including suspected ABC HSR (N = 3), renal failure (N = 2), decreased creatinine renal clearance (N = 1)
HEAT
Smith KY. AIDS 2009;23: 5

6. HEAT Study: ABC/3TC vs TDF/FTC
ARV-trial.com
HEAT Study: ABC/3TC vs TDF/FTC
Change in laboratory parameters (lipids, renal, biomarkers)
Median change from baseline at W96
ABC/3TC
TDF/FTC
Total cholesterol (mg/dL)
+ 36
+ 28
HDL-cholesterol (mg/dL)
+ 10
+ 12
Total cholesterol: HDL-cholesterol ratio
- 0.27
- 0.44
LDL-cholesterol (mg/dL)
+ 9
+ 8
Triglycerides (mg/dL)
+ 54
+ 42
GFR, MDRD equation (mL/min/1.73 m2)
Proximal renal tubular dysfunction occurrence
N = 0
N = 5 (1%)
Biomarkers (% change from baseline)
W48
W96
sVCAM-1
- 49
- 51
- 48
- 50
IL-6
- 26
- 19
- 23
- 25
hs-CRP
- 12
- 5
- 20
- 17
HEAT
Smith KY. AIDS 2009;23: 6

7. HEAT Study: ABC/3TC vs TDF/FTC
ARV-trial.com
HEAT Study: ABC/3TC vs TDF/FTC
Conclusions
As initial antiretroviral regimens, ABC/3TC and TDF/FTC, each in combination with LPV/r QD, have the same efficacy rate
HIV RNA responses by baseline HIV RNA strata (< or > 100,000 c/mL) were similar between groups at W48 and W96
Rate of virologic failure was similar in both groups (14%)
CD4 response at W96 was similar in the 2 groups
Both treatments were well tolerated
More gastrointestinal intolerance with TDF/FTC
More lipid abnormalities with ABC/3TC
Of note, rate of discontinuation was high (34% at W96)
Smith KY. AIDS 2009;23: 7