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. GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
ARV-trial.com
GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
Design
Randomisation*
1 : 1
Open-label
W48
> 18 years
ARV-naïve or < 2 weeks
of prior ARV exposure
HIV RNA > 10,000 c/mL
CD4 < 350/mm3
No active HBV infection
N = 167
SQV/r 1000/100 mg
BID
TDF/FTC fdc QD
N = 170
LPV/r 400/100 mg
BID
TDF/FTC fdc QD
SQV was administered as 500 mg tablet; LPV/r as soft-gel capsule,
changed to tablet when it became available
Objective
Non inferiority of SQV/r vs LPV/r at W48: % HIV RNA < 50 c/mL, ITT-Exposed, Missing = Failure (lower margin of the 1-sided 98% [equivalent to 2-sided 96%] CI for the difference = - 12%)
GEMINI
Walmsley S. JAIDS 2009;50:367-74 2

3. GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
ARV-trial.com
GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
Baseline characteristics and patient disposition
SQV/r N = 167
LPV/r N = 170
Median age, years 38 37
Female
19%
23%
White/Black/Other
50% / 30% / 20%
44% / 35% / 21%
HIV RNA (log10 c/mL), mean
HIV RNA > 100,000 c/mL
68%
64%
CD4 cell count (/mm3), median
142
CD4 < 100/mm3
40%
41%
Hepatitis C coinfection
9.6%
8.2%
Discontinuation before W48
39 (23%)
35 (21%)
GEMINI
Walmsley S. JAIDS 2009;50:367-74 3

4. GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
ARV-trial.com
GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
Response to treatment at week 48
% HIV RNA < 50 c/mL
Median CD4 (/mm3) increase
100
Primary efficacy
endpoint
204
SQV/r
200 80
178
LPV/r
64.7
65.5
63.5
62.1
160 60
120 40 80 20
N =
167
170
148
145 40
ITT-E,M = F
Per protocol
96% CI for the difference = - 9.6; 11.9
96% CI for the difference = - 8.1; 15.0
p = 0.33
Virologic failures (2 consecutive HIV RNA > 400 c/mL at W16 or after): 11 (7%) (SQV/r) vs 5 (3%) (LPV/r)
Emergence of M184V: 5/11 SQV/r vs 4/5 LPV/r; emergence of major PI mutations: 1 SQV/r vs 0 LPV/r
ITT-E, M = F: ITT-exposed, missing = failure
GEMINI
Walmsley S. JAIDS 2009;50:367-74 4

5. GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
ARV-trial.com
GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
Safety and tolerability: SQV/r vs LPV/r
Low frequency of premature discontinuations for adverse events: 3% vs 7%
Most frequent reported adverse events of any grade were gastrointestinal disorders: 17% vs 27%
No discontinuation because of renal-related adverse events; 2 patients, in the LPV/r arm, had elevated plasma creatinine levels > 2 mg/dL attributed to TDF/FTC
Median changes at W48 in total, LDL- and HDL-cholesterol were not significantly different between treatment groups; elevation of triglycerides was significantly higher in the LPV/r arm
GEMINI
Walmsley S. JAIDS 2009;50:367-74 5

6. GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
ARV-trial.com
GEMINI Study: SQV/r BID vs LPV/r BID, in combination with TDF/FTC
Conclusions
SQV/r BID was non inferior to LPV/r BID, in combination with TDF/FTC fdc
Virologic and immunologic responses were similar in both arms
Tolerability was similar in both arms
Gastrointestinal adverse events were more frequent with LPV/r
Lipid changes were not different between SQV/r and LPV/r except for triglycerides elevation, which was higher with LPV/r
Rate of virologic failure was low in both groups
1 patient in the SQV/r group developed new major protease resistance mutations at virologic failure
GEMINI
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