Transcript ARV-trials 2010

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
M02-418
M05-730
A5073
 LPV/r + 3TC vs LPV/r + 2 NRTI
GARDEL
 ATV/r vs FPV/r
ALERT
 FPV/r vs LPV/r
KLEAN
 SQV/r vs LPV/r
GEMINI
 ATV/r vs LPV/r
CASTLE
 DRV/r vs LPV/r
ARTEMIS
GEMINI Study: SQV/r BID vs LPV/r BID,
in combination with TDF/FTC
 Design
Randomisation*
1:1
Open-label
> 18 years
ARV-naïve or < 2 weeks
of prior ARV exposure
HIV RNA > 10,000 c/mL
CD4 < 350/mm3
No active HBV infection
 Objective
N = 167
N = 170
W48
SQV/r 1000/100 mg
BID
TDF/FTC fdc
QD
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
– 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
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
38
37
19%
23%
50% / 30% / 20%
44% / 35% / 21%
5.20 + 0.53
5.17 + 0.63
HIV RNA > 100,000 c/mL
68%
64%
CD4 cell count (/mm3), median
142
142
CD4 < 100/mm3
40%
41%
Hepatitis C coinfection
9.6%
8.2%
39 (23%)
35 (21%)
Median age, years
Female
White/Black/Other
HIV RNA (log10 c/mL), mean
Discontinuation before W48
GEMINI
Walmsley S. JAIDS 2009;50:367-74
GEMINI Study: SQV/r BID vs LPV/r BID,
in combination with TDF/FTC
Response to treatment at week 48
100
80
Median CD4 (/mm3) increase
% HIV RNA < 50 c/mL
Primary efficacy
endpoint
64.7 63.5
60
SQV/r
65.
5
62.1
204
200
LPV/r
178
160
120
40
80
20
N = 167 170
0
ITT-E,M = F
148 145
Per protocol
96% CI
96% CI
for the difference for the difference
= - 9.6; 11.9
= - 8.1; 15.0
40
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
GEMINI
ITT-E, M = F: ITT-exposed, missing = failure
Walmsley S. JAIDS 2009;50:367-74
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
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
Walmsley S. JAIDS 2009;50:367-74