GSUS2160114 Gallant JE JID 2013208329 GSUS2160114 Design Objective Non inferiority of COBI compared with RTV at W48 HIV RNA lt 50 cmL by intention to treat snapshot analysis lower limit for the 95 CI for the difference 12 95 power ID: 816610
Download The PPT/PDF document "Comparison of RTV vs Cobi" 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
Comparison of RTV vs Cobi
GS-US-216-0114
Slide2Gallant JE. JID 2013;208:32-9
GS-US-216-0114
Design
Objective
Non inferiority of COBI compared with RTV at W48: % HIV RNA < 50 c/mL
by intention to treat, snapshot analysis (lower limit for the 95% CI for the difference = -12%, 95% power)
COBI + RTV placebo + ATV 300 mg
+ FTC/TDF QD
COBI placebo + RTV + ATV 300 mg
+ FTC/TDF QD
Randomisation*
1 : 1Double-blind
> 18 yearsARV-naïve HIV RNA > 5,000 c/mLAny CD4 cell counteGFR > 70 mL/minSensitivity to ATV, FTCAnd TDF on genotype
* Randomisation was stratified by HIV RNA (< or > 100,000 c/mL) at screening
Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF
N = 348
N = 344
W48
W192
Slide3COBI + ATV + FTC/TDF
N = 344
RTV + ATV + FTC/TDF
N =
348
Mean
age, years
37
38
Female
17%
18%
HIV RNA (log
10
c/mL
),
median
4.78
4.84
HIV RNA
>
100,000
c/mL
38.4%41.1%CD4 cell count (/mm3), mean353351CD4 < 200 per mm312%16%Hepatitis B / hepatitis C coinfection5% / 6%3% / 5%Discontinuation by W4817%11%For lack of efficacyN = 2N = 0For adverse eventN = 25N = 25Lost to follow-upN = 11N = 4Non-complianceN = 43
Baseline characteristics and patient disposition
Gallant JE. JID 2013;208:32-9
GS-US-216-0114
Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF
Slide4HIV RNA < 50 c/mL
Mean CD4/mm
3
increase at W48 :
+ 213 COBI vs + 219 RTV
Response to treatment at week 48
Viral suppression was high in both treatment arms, for various
subgroups, including patients with
HIV RNA > 100,000 c/mL at baselineGallant JE. JID 2013;208:32-9
GS-US-216-0114Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF2550
10075
%
Adjusted difference(95% CI) =-2.2%( - 7.4 ; 3.0)98.0
Primary analysis
Adjusted
difference(95% CI)
=-0.1 % ( - 2.5 ; 2.3)
COBI + ATV + FTC/TDF
RTV + ATV + FTC/TDF
ITT, snapshot
Per protocol
98.0
85.2
87.4
0
Slide5Gallant JE. JAIDS 2015;69:338-40
GS-US-216-0114
Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF
Response to treatment at week 144 (ITT, snapshot)
Virologic success
Virologic failure
No data
HIV RNA < 50 c/mL
W48
W144
W48
W144
W48
W144
0
20
40
60
80
100
85
87
72
74
6
4
85992021%COBI + ATV + FTC/TDFRTV + ATV + FTC/TDFAdjusted difference(95% CI) =-2.1%( -8.7 ; 4.5)
Slide6Criteria for resistance testing :
confirmed HIV-1 RNA load rebound
of ≥ 400 c/mL or not obtaining HIV RNA < 400 c/mL by or after week 8
COBI + ATV + FTC/TDF
N = 344
RTV + ATV + FTC/TDF
N = 348
At W48
W48-W144
At W48
W48-W144
Analysed for the development of resistance
12 (3.5%)
9 (2.6%)
12 (3.4%)
7 (2.1%)
Available data
10
-
12
-
Emergent reverse transcriptase resistance
2
2
0
1
M184V211V118I010Emergent mutations to protease inhibitors0000Gallant JE. JID 2013;208:32-9 ; Gallant JE. JAIDS 2015;69:338-40GS-US-216-0114Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDFResistance data up to week 144
Slide7COBI + ATV + FTC/TDF
RTV + ATV + FTC/TDF
p
Jaundice
20.9%
15.5%
0.076
Scleral
icterus
17.7%
18.4%
-
Nausea
17.7%
16.4%
-
Diarrhea
15.4%
20.4%
0.093
Headache
11.0%
15.5%
0.093
Nasopharyngitis
10.8%15.2%0.09Hyperbiluribinemia11.3%9.8%Adverse events occurring in > 10% of patients in either group (W48)Gallant JE. JID 2013;208:32-9GS-US-216-0114Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDFCOBI + ATV + FTC/TDFRTV + ATV + FTC/TDFMedian increase of creatinine (mg/dL) at W48+ 0.13+ 0.09 (P < 0.001)Grade 3-4 hyperbilirubinemia65.3%56.6%Grade 3-4 elevation of ALT / AST3.2% / 2.9%2.0% / 2.0%Increase in total cholesterol (mg/dL) at week 48+ 5 + 9 (NS)
Increase in triglycerides (mg/
dL
) at week 48
+ 19
+ 32 (NS)
Laboratory abnormalities at W48
Slide8Adverse events leading to discontinuation of study drug
COBI + ATV + FTC/TDF
N = 344
RTV + ATV + FTC/TDF
N = 348
W48
W48-W144
W48
W48-W144
Total number of patients (%)
25 (7.3%)
9
25 (7.2%)
8
Scleral icterus
8
4
4
1
Jaundice
9
1
7
0
Hyperbilirubinemia
1
021Rash1000Allergic dermatitis2000Renal AEs645 6Gallant JE. JID 2013;208:32-9 ; Gallant JE. JAIDS 2015;69:338-40 GS-US-216-0114Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF Proximal renal tubulopathy7 in each groupIn 5 of the 7 patients in the COBI group and 6 of the 7 patients in the RTV group, PRT occurred after week 48
Slide920
10
0
-10
-20
-30
-40
BL
24
48
72
96
120
144
-15.1
-13.7
-12.9
-9.1
-8.3
-7.5
Week
GS-US-216-0114
Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF
Change in
eGFR
(mL/min), median [IQR]
Change in serum creatinine (mg/dL), median [IQR]
0.4
0.3
0.2
0.1
0.0
-0.1
-0.2
0.13
BL
24
48
72
96
120
144
0.07
0.08
0.09
0.13
0.12
Week
Serum
Creatinine
and
eGFR
Gallant JE. JAIDS 2015;69:338-40
COBI + ATV + FTC/TDF
RTV + ATV + FTC/TDF
Slide10No difference in TC:HDL ratio changes between arms (- 0.3
vs
-0.2)
Median
change
in fasting lipids at week 144 (mg/dL)
GS-US-216-0114
Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF
Gallant JE. JAIDS 2015;69:338-40
Total cholesterolLDL-cHDL-cTriglycerides
p = 0.35
p = 0.11
p = 0.11
p = 0.49
20
15
10
5
0
12
16
9
14
7
5
11
15COBI + ATV + FTC/TDFRTV + ATV + FTC/TDF
Slide11Summary
COBI was non inferior to RTV in combination with ATV plus FTC/TDF up to week 144
Both regimens
achieved high rates of virologic success
Safety and tolerability profiles of the 2 regimens were comparableOnce-daily COBI is a safe and effective pharmaco-enhancer of the protease inhibitor ATV
Renal safety was comparable between treatment armsDiscontinuation due to renal events was 2.9% in the COBI group and 3.2% in the RTV group at W144
Proximal renal tubulopathy occurred in 7 vs 7 patients (2.0%)A small, but significantly higher with COBI, increase in creatinine was seen in both groups, as early as week 2, with peak at week 8, and stabilization through 144 weeks
Gallant JE. JID 2013;208:32-9 ;
Gallant JE. JAIDS 2015;69:338-40
GS-US-216-0114Study GS-US-216-0114: ATV + ritonavir + FTC/TDF QD vs ATV + cobicistat + FTC/TDF