r 3TC OLE Study LPV r bid 3TC or FTC qd NRTI N 127 N 123 LPV r bid 3TCFTC qd Design Randomisation 1 1 Openlabel Objective Primary Endpoint proportion without treatment failure at W48 ID: 225862
Download Presentation The PPT/PDF document "Switch to LPV/" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Switch to LPV/r + 3TC
OLE
StudySlide2
LPV/
r
bid + 3TC or FTC
qd
+ NRTI
N =
127
N =
123
LPV/r bid + 3TC/FTC qd
Design
Randomisation*
1: 1Open-label
ObjectivePrimary Endpoint : proportion without treatment failure at W48 (ITT)Treatment failure : 2 consecutive HIV RNA ≥ 50 c/mL, death, new AIDS event, loss to follow-up, or change or permanent discontinuation of any antiretroviral drugNon-inferiority of dual therapy, upper limit of the 2-sided 95% CI for the difference = 12%, 80% power
Arribas JR. Lancet Infect Dis 2015;2015;15:785-92
≥ 18 yearsHIV-infected patientsStable LPV/r + 3TC or FTC + NRTI regimenHIV RNA < 50 c/mL > 6 monthsNo resistance to LPV/r, 3TC or FTC
W48
OLE
OLE Study: Switch to LPV/r + 3TC/FTC
*
Randomisation was stratified on time to HIV suppression (< or > 1
year
)
and nadir CD4 cell count (< or >
100/
m
l)Slide3
Baseline characteristics and disposition
LPV/
r
+ 2 NRTI
N = 121
LPV/
r
+ 3TC/FTC
N = 118
Median age, years
47
43
Female
36%
27%
Current CD4/mm
3, median
614
599
Nadir CD4/mm
3
, median
177175Duration of HIV RNA < 50 c/mL, median, months5044NRTI at screening, %TDF/FTCABC/3TCother602812622414Discontinuation at W48, NVirologic failureAdverse eventLost to follow-upMedical decision8 (7%)04318 (7%)1142
Arribas JR. Lancet Infect Dis 2015;2015;15:785-92
OLE Study: Switch to LPV/r + 3TC/FTC
OLESlide4
HIV RNA < 50 c/mL (ITT)
LPV/r + 3TC/FTC
LPV/r + 2 NRTI
Confirmed virologic failure
Efficacy results
at
W48
LPV/r + 2 NRTI
LPV/r + 3TC/FTC
N
3
3
Analyzed for resistance
2
2
Emergence of resistance
-
1 (K103N + M184V)
Causes of therapeutic failure
LPV/r + 2 NRTI
LPV/r + 3TC/FTC
Adverse
event3%1%Virologic failure2%2%Lost to follow-up2%3%Other6%6%Number of viral blips similar in both arms (N = 12)Arribas JR. Lancet Infect Dis 2015;2015;15:785-92OLE Study: Switch to LPV/r + 3TC/FTCOLETherapeutic response(ITT)No virologic failure(per protocol)0100
86.6 87.8
20
40
60
80
%
97.3
97.3
Difference
(
95
%
CI)
-
1.2
% (- 9.6 to
7.3)
Difference
(
95
%
CI)
0.1
% (- 5.1 to
5.3)Slide5
LPV/r + 2 NRTI
N = 121
LPV/r + 3TC/FTC
N = 118
Grade 3-4 adverse
event
s, N
8
10
Serious adverse
events, N
9
6
AEs leading to discontinuation, N4
Bone markers elevationHip aseptic necrosisOsteopenia + renal tubulopathyRenal function worsening
1Fanconi syndromeGrade 3-4 laboratory abnormalities, %
AST > 5 x ULN
2%
0
ALT > 5 x ULN
1%
3%
Cholesterol > 300 mg/dl (7.8 mmol/l)4%4%Triglycerides > 750 mg/dl (8.47 mmol/l)1%1%Safety at W48Small but significant increase of eGFR (MDRD), total and LDL cholesterol in the dual treatment group at 48 weeks compared with the triple treatment groupArribas JR. Lancet Infect Dis 2015;2015;15:785-92OLE Study: Switch to LPV/r + 3TC/FTCOLESlide6
Conclusion
In
virologically
suppressed patients on a triple-drug antiretroviral regimen with LPV/r + 2NRTI, switching to LPV/r + 3TC or FTC demonstrated non-inferior efficacy and comparable safety to LPV/r + 2 NRTI, as maintenance therapyPercentage of patients with protocol defined virological failure were very small and similar between arms
Dual therapy with LPV/r + 3TC or FTC has the potential benefit of preserving future options, reducing the cost of antiretroviral therapy and minimizing potential long term toxicity
OLE
Arribas JR. Lancet Infect Dis 2015;2015;15:785-92
OLE Study: Switch to LPV/r + 3TC/FTC