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. ARV-trial.com
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine
Design
Randomisation*
1 : 1
Open-label
W48
W144
TDF 300 mg QD
FTC 200 mg
EFV 600 mg
N = 255
517 ARV-naïve patients
> 18 years
HIV RNA > 10,000 c/mL
Any CD4 cell count
N = 254
ZDV/3TC 300/150 mg
BID
EFV 600 mg QD
*Randomisation was stratified on CD4 cell count < 200 or > 200/mm3
Objective
Non inferiority of TDF + FTC + EFV vs ZDV/3TC + EFV at W48: % HIV RNA < 400 c/mL, TLOVR algorithm (lower margin of the 95% CI for the difference = -13%, 85% power)
Study 934
Gallant JE. NEJM 2006;354:251-60 2

3. Baseline characteristics
ARV-trial.com
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine
Baseline characteristics
TDF + FTC
ZDV/3TC fdc
Randomized, N
258
259
Treated eligible patients, N
255
254
Median age, years 36 37
Female
14%
13%
White/Black/Other
56% / 25% / 19%
61% / 20% / 19%
HIV RNA (log10 c/mL), median
5.0
HIV RNA > 100,000 c/mL
52%
50%
CD4 cell count (/mm3), median
233
241
CD4 < 200/mm3
42%
41%
CD4 < 50/mm3
15%
11%
Baseline NNRTI resistance mutations, N
11*
* Excluded from primary endpoint analysis
Note : TDF, FTC and EFV taken without regards to meals and preferably at bed time;
Substitution of NVP for EFV allowed if EFV intolerance; not considered as treatment failure
Study 934
Gallant JE. NEJM 2006;354:251-60 3

4. Response to treatment at week 48
ARV-trial.com
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine
Response to treatment at week 48
Primary endpoint %
TDF + FTC
ZDV/3TC
/mm3
100
200
190 84 80 77
158 80 73
160 70 68 60
120 40 80 20 40
N =
244
243
244
243
255
254
HIV RNA < 400 c/mL
TLOVR
HIV RNA < 50 c/mL
TLOVR
HIV RNA < 50 c/mL
ITT
Mean CD4
increase
(p = 0.002)
95% CI for
the difference
= 4; 19
(p = 0.002)
95% CI for
the difference
= 2; 17
(p = 0.02)
95% CI for
the difference
= 1; 16
(p = 0.03)
Study 934
Gallant JE. NEJM 2006;354:251-60 4

5. ARV-trial.com
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine
Safety and tolerability: TDF + FTC vs ZDV/3TC
Similar frequency of clinical adverse events grade 2 to 4 and laboratory abnormalities grade 2 to 4 in both groups, respectively 63% vs 63% and 56% vs 57%
Significantly more discontinuations for adverse events in the ZDV/3TC group: 9% vs 4% (p = 0.02); mainly for anemia (N = 14 vs 0)
Renal safety was similar in both groups and no patients discontinued because of renal events. Change in median GFR (MDRD) at W48 was similar in both groups (< - 1 mL/min/1.73 m2). No Fanconi’s syndrome occurred
Mean increase significantly lower in the TDF + FTC group for total cholesterol, LDL-cholesterol and HDL-cholesterol; increase in triglycerides modest and not different between groups
At week 48, DEXA substudy in 100 patients (no baseline evaluation): significantly less total limb fat with ZDV/3TC (mean 6.9 vs 8.9 kg; p = 0.03)
Study 934
Gallant JE. NEJM 2006;354:251-60 5

6. ARV-trial.com
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine
Resistance data
Genotypic analysis was done in patients without baseline NNRTI resistance if
viral rebound (2 consecutive HIV RNA > 400 c/mL after achieving < 400 c/mL
HIV RNA > 400 c/mL at W48
discontinuation before W48 with HIV RNA > 400 c/mL at the last visit
Patients with baseline resistance (11 in each group) were excluded from this analysis of resistance
TDF + FTC N = 244
ZDV/3TC N = 243
Patients in genotypic analysis 12
23 *
Wild-type 3 5
Any resistance mutation 9 17
K65R
M184V/I 2 7
TAM 1
EFV resistance mutation ** 16
EFV resistance mutation + M184V 6
* 1 technical failure; ** K103N mutation developed in 21 of 25 patients
Study 934
Gallant JE. NEJM 2006;354:251-60 6

7. ARV-trial.com
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine
Study extended to 3 years of follow-up (W144)
At week 96, patients on TDF + FTC swithed to fixed-dose combination TDF/FTC
Results at week 144
TDF/FTC
ZDV/3TC p
HIV RNA < 400 c/mL
71%
58%
0.004
HIV RNA < 50 c/mL
64%
56%
0.08
CD4 increase (/mm3)
312
271
0.09
Discontinuation for virologic failure 2% 6%
0.038
Discontinuation for adverse events* 5%
11%
0.01
Median GFR (MDRD) W144 minus baseline (mL/min/1.73m2)
- 12
+ 1
< 0.001
Mean total limb fat (DEXA)
7.9 kg
5.4 kg
* No discontinuation for renal events
Study 934
Arribas JR. JAIDS 2008;47:74-8 7

8. ARV-trial.com
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine
Conclusions
TDF + FTC + EFV is non inferior to ZDV/3TC + EFV
Greater virologic response rates to TDF + FTC + EFV as compared with ZDV/3TC + EFV
Significantly greater CD4 response with TDF + FTC
Greater tolerability of TDF + FTC
This study shows superior outcome in the tenofovir-emtricitabine group
At week 144, TDF/FTC + EFV demonstrates superior durability of viral load suppression and an improved safety and morphologic profile compared with ZDV/3TC and EFV
Study 934
Gallant JE. NEJM 2006;354:251-60; Arribas JR. JAIDS 2008;47:74-8 8