Transcript the slides - ARV

Comparison of PI vs PI
 ATV vs ATV/r
 LPV/r mono vs LPV/r + ZDV/3TC
 LPV/r QD vs BID
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LPV/r + 3TC vs LPV/r + 2 NRTI
ATV/r vs FPV/r
ATV/r vs DRV/r
FPV/r vs LPV/r
SQV/r vs LPV/r
ATV/r vs LPV/r
DRV/r vs LPV/r
BMS 089
MONARK
M02-418
M05-730
A5073
GARDEL
ALERT
ATADAR
KLEAN
GEMINI
CASTLE
ARTEMIS
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI
 Design
Randomisation*
1:1
Open-label
> 18 years
ARV-naïve
HIV RNA > 1,000 c/mL
Any CD4 cell count
HBsAg negative
No R to study drugs
N = 217
N = 209
W48
W96
LPV/r 400/100 mg + 3TC 150 mg BID
LPV/r 400/100 mg BID + FDC
of 2 NRTI**
*Randomisation was stratified by HIV RNA (<or > 100,000 c/mL) at screening
** Investigator-selected NRTI : ZDV/3TC = 54%, TDF/FTC = 37%, ABC/3TC = 9%
 Objective
– Non inferiority of LPV/r + 3TC at W48: % HIV RNA < 50 c/mL by intention
to treat, snapshot analysis (lower limit of the 95% CI for the difference = -12%,
85% power)
GARDEL
Cahn P. Lancet Infect Dis 2014;14:572-80
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI
Baseline characteristics and patient disposition
LPV/r + 3TC
N = 214
LPV/r + 2 NRTI
N = 202
34
35
Female
16%
17%
HIV RNA (log10 c/mL), median
4.87
4.87
HIV RNA > 100,000 c/mL
44%
43%
CD4 cell count (/mm3), median
319
329
CD4 < 200 per mm3
21%
19%
16 (7.5%)
27 (13.4%)
For virologic failure at week 24
N=1
N=6
For adverse event
N=1
N = 10
Lost to follow-up
N=7
N=9
Non-compliance
N=5
N=1
Death
N=1
0
0
N=1
N=1
0
Median age, years
Discontinuation by W48
Opportunistic infection
Pregnancy
GARDEL
Cahn P. Lancet Infect Dis 2014;14:572-80
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI
Response to treatment at week 48
HIV RNA < 50 c/mL
%
100
Primary analysis
All patients
88.3
83.7
Baseline HIV-1 RNA
≥ 100 000 c/mL
All patients
95.5
96.6
LPV/r + 3TC
LPV/r + 2 NRTI
87.2
77.9
75
50
Median CD4/mm3
increase :
+ 227 (LPV/r + 3TC) vs
+ 217 (LPV/r + 2 NRTI)
25
0
GARDEL
ITT, snapshot
ITT, snapshot
Observed
Adjusted difference
(95% CI)=
4.6% (- 2.2 ; 11.8)
Adjusted difference
(95% CI)=
9.3%(- 2.8 ; 21.5)
Adjusted difference
(95% CI)=
- 1.1% (- 5.6 ; 3.4)
Cahn P. Lancet Infect Dis 2014;14:572-80
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI
 Virologic failure definition
- 2 consecutive HIV-1 RNA > 400 c/mL at or after W24
- HIV-1 RNA > 50 c/mL at W48
Resistance data at week 48
LPV/r + 3TC
LPV/r + 2 NRTI
Virologic failure
10
12
At week 24
1
6
At week 48
9
6
Median HIV-1 RNA at virologic failure, c/mL
236
1027
Success of amplification for genotype testing
5/10
7/12
2
0
2
0
-
Presence of resistance mutations
M184V
Protease inhibitor resistance
GARDEL
Cahn P. Lancet Infect Dis 2014;14:572-80
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI
 Adverse events
LPV/r + 3TC
LPV/r + 2NRTI
P
Grade 2-3 AE possibly or probably drug related
65 (30%)
88 (44%)
0.007
Patients with grade 2-3 AE possibly or probably
drug related
43
48
-
Hyperlipidaemia
23
16
-
Diarrhoea
14
14
-
Nausea
2
9
0.05
Dyspepsia
2
6
0.02
2 (1%)
11 (5%)*
0.01
0
11
10
(anaemia = 3,
GI, N = 6, rash = 1)
1 (rash)
Drug-related AE ≥ 2% in either group
AE leading to discontinuation
NRTI related
- Zidovudine
- Tenofovir
Selected grade 3-4 laboratory abnormalities occurred at the same frequency in both groups,
except for hyperlipidemia (more frequent in dual therapy group)
GARDEL
Cahn P. Lancet Infect Dis 2014;14:572-80
GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI
 Summary
– LPV/r + 3TC dual therapy was virologically non inferior to a standard
therapy of LPV/r + 2 NRTI
– Similar virologic response of the 2 regimens in patients with HIV
RNA > 100 000 c/mL at enrolment
– No resistance mutations to protease inhibitor at virologic failure in either
group
• 2 patients with M184V in dual therapy group
– Incidence of adverse events higher in triple therapy group
– Discontinuation because of adverse events mainly related to NRTI in
the LPV/r + NRTI arm
– Potential advantages of first-line LPV/r + 3TC
• Cost
• Less toxicity (might need less monitoring)
• Spares the other NRTIs
GARDEL
Cahn P. Lancet Infect Dis 2014;14:572-80