Transcript HARNESS Study: switch to ATV/r + RAL - ARV

Switch to ATV/r + RAL
 HARNESS Study
HARNESS Study: switch to ATV/r + RAL
 Design
Randomisation
2:1
Open-label
Adults
Stable 2 NRTI + 3rd drug regimen
No previous treatment failure
HIV RNA < 40 c/mL > 3 months
Switch for safety and/or
tolerability issues
No resistance to study medications
HBs Ag negative
N = 37
W24
W48
ATV/r 300/100 mg qd + TDF/FTC
ATV/r 300/100 mg qd + RAL 400 mg bid
N = 72
 Objective
– Primary Endpoint: proportion with treatment success at W24
(HIV-1 RNA < 40 c/mL)
• No power calculation
• Descriptive analysis
HARNESS
Van Lunzen J. JAIDS 2016;71:538-43
HARNESS Study: switch to ATV/r + RAL
Baseline characteristics and disposition
ATV/r + TDF/FTC
N = 37
ATV/r + RAL
N = 72
44
44
Female
16%
19%
Baseline CD4/mm3, mean
631
588
ARV regimens prior to switch
PI/r + 2 NRTI
NNRTI + 2 NRTI
Other ARV regimens
54%
38%
8%
44%
51%
4%
5
1
1
16
4
3
Median age, years
Discontinuation at W48, N
Adverse event
Lack of efficacy
HARNESS
Van Lunzen J. JAIDS 2016;71:538-43
HARNESS Study: switch to ATV/r + RAL
Efficacy and Safety results
HIV RNA < 40 c/mL (ITT)
ATV/r + TDF/FTC
W24
(primary endpoint)
ATV/r + RAL
ATV/r + TDF/FTC
ATV/r + RAL
N
1
9
Tested isolates
0
5
PI resistance
1*
L10V, G16Q, L33F,
P39Q, M46L, G48V,
Q58E, I62V, L63I/T,
I64L, A71V, I72V, V77I,
V82A, T91S, I93L
INI resistance
2*
F21Y
Y143C + N155H
W48
%
100
Confirmed virologic rebound at W48, N
94.6
86.5
80
80.6
69.4
60
* 1 patient with both PI and INSTI mutations
40
20
0
HARNESS
 Virologic rebound
̶
̶
2 consecutive on-treatment HIV RNA > 40 c/mL
Last on-treatment HIV RNA > 40 c/mL followed by
discontinuation
Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19, Van Lunzen J. JAIDS 2016;71:538-43
HARNESS Study: switch to ATV/r + RAL
Time to treatment failure (discontinuation of study therapy
before W48 or virologic rebound before or at W48)
Kaplan-Meier estimate
%
100
80
60
40
ATV/r + TDF/FTC
ATV/r + RAL
20
0
B/L
4
8
12
HARNESS
20
24
28
32
36
40
44
48
52
Week
Number of patients at risk
ATV/r + RAL
ATV/r + TDF/FTC
16
72
37
68
37
67
35
64
35
57
35
54
34
39
25
Van Lunzen J. JAIDS 2016;71:538-43
HARNESS Study: switch to ATV/r + RAL
Safety at W48, N
ATV/r + TDF/FTC
ATV/r + RAL
N = 37
N = 72
Grade 3-4 AEs
5
13
Grade 2-4 drug-related AEs
8
12
Grade 3-4 total bilirubin
3
5
Renal toxicity
6
1
Discontinuation due to AE
1
4
 ATV and RAL geometric mean Ctrough values, available for most
patients, were within therapeutic ranges over the study course
HARNESS
Van Lunzen J. JAIDS 2016;71:538-43
HARNESS Study: switch to ATV/r + RAL
 Conclusion
– In virologically suppressed patients on a triple-drug antiretroviral
regimen, switching to ATV/r + RAL resulted in a lower maintenance
of virologic suppression and a higher incidence of virologic rebound
than in the ATV/r + TDF/FTC group at Week 24 and Week 48
– In addition, tolerability issues and treatment discontinuation occurred
more frequently and adherence was lower with ATV/r + RAL
– This pilot study did not support switching to ATV/r + RAL for
safety/tolerability reasons in treatment-experienced patients with
virological suppression
HARNESS
Van Lunzen J. JAIDS 2016;71:538-43