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. ARV-trial.com
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Design
Randomisation*
1 : 1
Open-label
W48
W192
N = 343
DRV/r 800/100 mg QD
TDF/FTC fdc QD
> 18 years
ARV-naïve
HIV RNA > 5,000 c/mL
Any CD4 cell count
LPV/r 400/100 mg BID
or 800/200 mg QD
TDF/FTC fdc QD
N = 346
*Randomisation was stratified by HIV RNA (< or > 100,000 c/mL) and CD4 (< or > 200/mm3) at screening
Objective
Non inferiority of DRV/r vs LPV/r at W48: % HIV RNA < 50 c/mL by per-protocol TLOVR analysis (lower margin of the 2-sided 95% CI for the difference = - 12%, 90% power). Superiority tested by ITT if non inferiority established
ARTEMIS
Ortiz R. AIDS 2008;22: 2

3. Baseline characteristics and patient disposition
ARV-trial.com
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Baseline characteristics and patient disposition
DRV/r N = 343 *
LPV/r ** N = 346
Mean age, years 36 35
Female
30%
Caucasian/Hispanic/Other
40% / 23% / 37%
44% / 21% / 35%
HIV RNA (log10 c/mL), mean
CD4 cell count (/mm3), median
228
218
Hepatitis B and/or C coinfection
13%
14%
Discontinuation by W48
12%
16%
For virologic failure
2 (< 1%)
6 (2%)
For adverse event
12 (3%)
24 (7%)
* 3 patients excluded for the per-protocol analysis (did not received study medication
or received disallowed therapy for more than 1 week)
** LPV/r was administered BID or QD according to investigator and/or patient preference
(77% received BID, 15% QD and 8% both; 15% received soft-gel capsules, 2% tablets
and 83% switched from SGC to tablets)
ARTEMIS
Ortiz R. AIDS 2008;22: 3

4. Response to treatment at week 48
ARV-trial.com
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Response to treatment at week 48
HIV RNA < 50 c/mL (TLOVR) 25 50
100 75 84 78
343 %
DRV/r
LPV/r
346
95% CI for the difference
= (- 0.1; 11) (P < 0.001)
 Non inferiority
Per protocol
ITT
= (- 0.3; 11)
Test for superiority
(P = 0.062)
N =
ARTEMIS
HIV RNA < 50 c/mL at W48 (per-protocol, TLOVR) by baseline stratification factors
Baseline
DRV/r (%)
LPV/r (%)
RNA < 5 log10 c/mL
RNA > 5 log10 c/mL 86
79 * 85
67 *
CD4 > 200/mm3
CD4 < 200/mm3 87 79 84 70
* P < 0.05
Median CD4/mm3 increase at W48 (ITT, NC = F):
137 (DRV/r) vs 141 (LPV/r)
Ortiz R. AIDS 2008;22: 4

5. ARV-trial.com
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Virologic failure at Week 48
Definition: HIV RNA never suppressed below 50 c/mL at W24
or confirmed HIV RNA > 50 c/mL after achieving < 50 c/mL
or last observed HIV RNA > 50 c/mL followed by discontinuation
Resistance data
DRV/r N = 343
LPV/r N = 346
Virologic failure
34 (10%)
49 (14%)
Patients in genotypic analysis (HIV RNA > 1,000 c/mL)
10 * 18
Protease inhibitor resistance mutation emergence
1 **
M184I/V 1 2
* 1 patient with HIV RNA > 1,000 c/mL did not have genotype available
** A71T and V77I
ARTEMIS
Ortiz R. AIDS 2008;22: 5

6. ARV-trial.com
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
W48 Safety: DRV/r vs LPV/r
Discontinuations for adverse events (AE) were significantly less frequent in the DRV/r group: 3% vs 7% (P < 0.05)
Rate of serious AE was not significantly different: 7% vs 12%
Incidence of grade 2 to 4 gastrointestinal AE was significantly lower in the DRV/r group: 7% vs 14% (P < 0.01); these were mainly diarrhoea: 4% vs 10% (P < 0.01)
Rash incidence was not significantly different: 3% vs 1%; 1 case of Stevens-Johnson occurred in the DRV/r group
No patients discontinued because of renal events
Mean increases in triglycerides and total cholesterol were less pronounced with DRV/r; grade 2 to 4 elevations in triglycerides and total cholesterol were significantly less frequent with DRV/r: 3% vs 11% and 13% vs 23%, respectively
Hepatic safety was similar in both groups
ARTEMIS
Ortiz R. AIDS 2008;22: 6

7. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Summary – Conclusion (W48)
DRV/r QD is non inferior to LPV/r, when co-administered with TDF/FTC(1)
Greater virologic response, at W48 (HIV RNA < 50 c/mL), of DRV/r as compared with LPV/r in patients with high pre treatment HIV RNA (significant difference) or low CD4 count
Lower incidence of diarrhoea with DRV/r vs LPV/r
Lipid elevations were less pronounced with DRV/r
Ortiz R. AIDS 2008;22:

8. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Overview at week 96
At W96(2), significantly more DRV/r (79%) than LPV/r (71%) patients had HIV RNA < 50 c/mL confirming non inferiority and superiority (P = 0.012; ITT) in virologic response
Safety outcomes confirmed W48 results: more favourable gastrointestinal and lipid profile of DRV/r QD
Lipid-lowering agents use by W96: 8% LPV/r vs 7% DRV/r
Overall, discontinuation for adverse events occurred in 4% of DRV/r patients vs 9% of LPV/r patients
Mills AM. AIDS 2009;23:

9. Patient disposition at W96 and W192
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Patient disposition at W96 and W192
DRV/r N = 343
LPV/r N = 346 p
Discontinuation by W48
12%
16%
For virologic failure
2 (< 1%)
6 (2%)
For adverse event
12 (3%)
24 (7%)
Discontinuation by W96
17.2%
23.4%
Discontinuation by W192
24.8%
32.9% 5 9
16 (4.7%)
44 (12.7%)
0.005
For pregnancy 6
Lost to follow-up 21 17
Withdrew consent/non compliance 26
Other 8 12
ARTEMIS
Ortiz R. AIDS 2008;22: ; Mills AM. AIDS 2009;23: ; Orkin C. HIV Med 2012;14:49-59

10. ARV-trial.com
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Final (week 192) analysis 25 50
100 75
69.1
57.1
340 %
DRV/r
LPV/r
345
Difference (95% CI)
= 12.0% (4.8 ; 19.2)
(P < 0.001)
 Superiority
68.8
57.2
343
346
Per protocol
ITT
N =
= 11.6% (4.4 ; 18.8)
HIV RNA < 50 c/mL (TLOVR)
HIV RNA < 50 c/mL (ITT, TLOVR) by baseline stratification factors
Baseline
DRV/r (%)
LPV/r (%) p
RNA < 5 log10 c/mL
RNA > 5 log10 c/mL
69.5
67.5
60.2
51.7
0.038
0.012
CD4 > 200/mm3
CD4 < 200/mm3
71.3
65.2
59.6
54.1
0.014
0.052
Median CD4/mm3 increase at W192 (ITT, NC = F):
+ 258 (DRV/r) vs (LPV/r)
ARTEMIS
Orkin C. HIV Med 2012;14:49-59 10

11. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Resistance data at W192
DRV/r N = 343
LPV/r N = 346
Virologic failure
55 (16.0%)
71 (20.5%)
Never suppressed 16 22
Rebounders 39 49
Resistance testing (HIV RNA > 50 c/mL) 43 57
Protease inhibitor resistance mutation emergence*
Major PI mutation
4** 9
NRTI resistance mutations * 4
M184I/V = 4
K70E = 1 7
M184I/V
* At endpoint = last time point : with available genotype
** L10V, N = 1 ; V11I, N = 1 ; I13V, N = 1 ; I13V + G16E, N = 1
ARTEMIS
Orkin C. HIV Med 2012;14:49-59

12. ARV-trial.com
ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD), in combination with TDF/FTC
Safety – W192 analysis
Data similar to that seen at W96
No new emerging AE with longer-term follow-up
Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003)
DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low- and high-density lipoprotein cholesterol were similar between groups
Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed
ARTEMIS
Orkin C. HIV Med 2012;14:49-59 12