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 M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
ARV-trial.com
Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
Design
Randomisation
1:1:1:1
Open-label W8
W48
W96
N = 166
LPV/r tablet BID
+ TDF + FTC
LPV/r tablet BID
+ TDF + FTC
N = 331
N = 165
LPV/r SGC BID
+ TDF + FTC
664 patients > 18 years
ARV-naïve
HIV RNA > 1,000 c/mL
N = 167
LPV/r tablet QD
+ TDF + FTC
LPV/r tablet QD
+ TDF + FTC
N = 333
N = 166
LPV/r SGC QD
+ TDF + FTC
Objective
Primary endpoint: HIV RNA < 50 c/mL at W48 (ITT, NC = F)
Non-inferiority of LPV/r QD vs BID if lower margin of the 95% CI for the difference = - 12% (> 90% power)
LPV/r dose: 400/100 mg BID or 800/200 mg QD
M05-730
Gathe J. JAIDS 2009;50:474-81 2

3. Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
ARV-trial.com
Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
Patient disposition and baseline characteristics
LPV/r QD
LPV/r BID
Randomized, N
337
335
Treated eligible patients, N
333
331
Mean age, years
Female
20.1%
23.3%
White/Black
78% / 17%
73% / 20%
HIV RNA (log10 c/mL), mean
4.93
5.05 (p = 0.02 vs QD)
HIV RNA > 100,000 c/mL
48%
58.3% (p = vs QD)
CD4 cell count (/mm3), mean
216
215
CD4 < 200/mm3
45%
46%
Discontinuation by W48, N (%)
49 (15%)
55 (17%)
For adverse event 16 10
For virologic failure 2 5
Lost to follow-up/withdrew consent/ non adherence/death
10/16/
5/2
17/13/
9/1
M05-730
Gathe J. JAIDS 2009;50:474-81 3

4. Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
ARV-trial.com
Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
Response to treatment at week 48
QD (N = 333)
BID (N = 331)
Mean CD4 increase at W48: 186/mm3 (QD) vs 198/mm3 (BID) (p = 0.32)
Sensitivity ITT, NC = F, analysis adjusting for baseline imbalance in HIV RNA level confirms non inferiority of virologic response (95% CI for the difference = - 6; 7)
Sub-group post hoc analyses:
% HIV RNA < 50 c/mL similar at W48 with QD and BID LPV/r, according to subgroups defined by baseline HIV RNA (< or > 100,000 c/mL) or CD4 count (< 50, 50 to < 200 or > 200/mm3)
for patients with baseline HIV RNA > 100,000 c/mL and CD4 < 200/mm3, HIV RNA < 50 c/ml = 74% QD vs 73 % BID
Primary efficacy endpoint %
100 90 87 77 76 80 60 40 20
ITT, NC = F
Observed data
95% CI for the difference
= - 5; 8
95% CI
for the difference
= - 8; 3
M05-730
Gathe J. JAIDS 2009;50:474-81 4

5. Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
ARV-trial.com
Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
Adverse events and resistance
LPV/r QD (N = 333)
LPV/r BID (N = 331) p
Adverse events of at least moderate severity related to study drugs
Diarrhoea
17%
15% NS
Nausea 7% 5%
Vomiting 3% 4%
Grade 3/4 laboratory abnormalities
AST > 5 x ULN 1% 2%
Cholesterol > 300 mg/dL
Triglycerides > 750 mg/dL 6%
0.063
Creatinine clearance < 50 mL/min
During the first 8 weeks of treatment
Clinical (gastrointestinal) and laboratory (lipids) tolerability similar for SGC and tablets
Resistance
Among 17 subjects (10 QD and 7 BID) tested for resistance (HIV RNA > 50 c/mL at or after W24 and confirmed > 400 c/mL within 4 weeks): no emergence of PI or TDF resistance mutations. M184V emergence in 3 patients (2 QD, 1 BID)
M05-730
Gathe J. JAIDS 2009;50:474-81 5

6. Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
ARV-trial.com
Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD
Summary - Conclusion
In antiretroviral-naïve adults, LPV/r QD was virologically non inferior at W48 to LPV/r BID, when administered in combination with TDF and FTC
During the first 48 weeks of therapy, there were no significant differences in the safety or tolerability of QD vs BID LPV/r
This study used LPV/r tablets, and did not show differences in rate of diarrhoea between QD and BID dosing
In subgroups with high baseline HIV RNA and/or low CD4 count, efficacy of LPV/r QD and BID was similar
Absence of resistance emergence to LPV/r or TDF, in either groups
Limited and similar lipid impact of both LPV/r dosing
Patient preference of the tablet over the soft-gel capsule
Results support the use of LPV/r QD in combination with TDF and FTC in antiretroviral-naive patients
M05-730
Gathe J. JAIDS 2009;50:474-81 6