1. Comparison of PI vs PI ATV vs ATV/r BMS 089
ARV-trial.com
Comparison of PI vs PI
ATV vs ATV/r BMS 089
LPV/r mono vs LPV/r + ZDV/3TC MONARK
LPV/r QD vs BID M M A5073
LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL
ATV/r vs FPV/r ALERT
ATV/r vs DRV/r ATADAR
FPV/r vs LPV/r KLEAN
SQV/r vs LPV/r GEMINI
ATV/r vs LPV/r CASTLE
DRV/r vs LPV/r ARTEMIS 1

2. Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
ARV-trial.com
Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
Design
Randomisation*
1 : 1
Open-label
W48
200 adults
ARV-naïve or < 30 days of
prior NRTI or < 7 days of
prior NNRTI or PI
HIV RNA > 2,000 c/mL
Any CD4 cell count
ATV/r 300/100 mg QD
3TC + d4T XR
N = 95
N = 105
ATV 400 mg
BID
3TC + d4T XR QD
*Randomisation was stratified on HIV RNA < or > 100,000 c/mL
Objective
Non inferiority of ATV/r 300/100 vs ATV 400 at W48:
% HIV RNA < 400 c/mL, ITT, TLOVR algorithm (lower margin of the 95% CI for the difference = -10%, 80% power)
BMS 089
Malan DR. JAIDS 2008;47:161-7 2

3. Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
ARV-trial.com
Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
Baseline characteristics and patient disposition
ATV/r 300/100 mg
ATV 400 mg
Randomized, N 95
105
Treated eligible patients, N
104
Median age, years 35 34
Female
27%
30%
White/Black/Other
53% / 26% / 21%
57% / 26% / 17%
HIV RNA (log10 c/mL), median
4.8
5.1
HIV RNA > 100,000 c/mL
42%
52%
CD4 cell count (/mm3), median
201
194
CD4 < 200/mm3
48%
Hepatitis B and/or C positive
18%
19%
Discontinuation before W48
12%
10%
BMS 089
Malan DR. JAIDS 2008;47:161-7 3

4. Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
ARV-trial.com
Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
Response to treatment at week 48 (ITT, TLOVR)
Primary endpoint
ATV/r (N = 95)
ATV (N = 105) %
HIV RNA < 400 c/mL
HIV RNA < 50 c/mL
HIV RNA < 50 c/mL
100 86 85 87 82 80 75 70 63 58 60 40 20
N = 46 50 49 55
All patients
Baseline HIV RNA < 100,000 c/mL
Baseline HIV RNA > 100,000 c/mL
95% CI
for the difference
= - 8.2; 11.1
95% CI for the difference
= - 7; 17
Median CD4 increase at W48: 174/mm3 (ATV/r) vs 213/mm3 (ATV)
BMS 089
Malan DR. JAIDS 2008;47:161-7 4

5. Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
ARV-trial.com
Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
Treatment-emergent resistance
Genotypic and phenotypic resistance in patients with virologic failure through W48
ATV/r
ATV
HIV RNA > 400 c/mL
N = 3
N = 10
Resistance testing
N = 2
N = 8
PI major substitutions
I50L, N88S
1 #
I50I/L 2
PI minor substitutions * 1 4
ATV phenotype: FC > 2.2
1 (FC = 26) #
M184V 7
# Same patient; * Among 20I/T, 33F, 34Q, 36V, 64V, 71V, 73S, 74A, 83D
BMS 089
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6. Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
ARV-trial.com
Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
Safety
ATV/r
ATV
Serious adverse event
15%
16%
Discontinuation for adverse event 8%
< 1%
Grade 2 to 4 treatment-related adverse event
43%
34%
Jaundice 3%
Grade 3-4 laboratory abnormality
Total bilirubin > 2.5 x ULN
59%
20%
ALT > 5 x ULN 6%
AST > 5 x ULN
Total cholesterol > 300 mg/dL 1%
Triglycerides > 751 mg/dL 2%
Upward shift of > 1 NCEP category at W48 for ATV/r vs ATV:
total cholesterol: 16% vs 11%
LDL-cholesterol: 46% vs 48%
triglycerides: 30% vs 18%
BMS 089
Malan DR. JAIDS 2008;47:161-7 6

7. Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
ARV-trial.com
Study BMS 089: ATV vs ATV/r QD, in combination with 3TC + d4T XR QD
Summary - Conclusion
For first-line antiretroviral therapy, ATV/r 300/100 mg QD was virologically non inferior to ATV 400 mg QD, when combined with 3TC and d4T XR QD
Response rate at an HIV RNA < 50 c/mL at W48 was 25% less in patients with baseline HIV RNA > 100,000 c/mL as compared with baseline HIV RNA < 100,000 c/mL
Virologic failure occurred more frequently in the ATV group (9.5% vs 3.2%) with emergence of major atazanavir-associated mutations in 3/8 tested patients in the ATV group
Results (HIV RNA < 50 c/mL at W48, virologic failure rate, resistance data) suggest ATV/r is more potent than ATV
Discontinuation due to treatment-related adverse event occurred more frequently in the ATV/r group
Increases in total cholesterol and triglycerides were greater in the ATV/r group
Possible impact of stavudine on lipid increases
Limitation: small size of the study
BMS 089
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