1. ARV-trial.com
Switch to ATV/r + RAL
HARNESS Study 1

2. HARNESS Study: switch to ATV/r + RAL
Design
Randomisation
2 : 1
Open-label
W24
W48
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
ATV/r 300/100 mg qd + TDF/FTC
N = 37
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

3. Baseline characteristics and disposition
HARNESS Study: switch to ATV/r + RAL
Baseline characteristics and disposition
ATV/r + TDF/FTC
N = 37
ATV/r + RAL
N = 72
Median age, years 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%
Discontinuation at W48, N
Adverse event
Lack of efficacy 5 1 16 4 3
HARNESS
Van Lunzen J. JAIDS 2016;71:538-43

4. HARNESS Study: switch to ATV/r + RAL
Efficacy and Safety results
HIV RNA < 40 c/mL (ITT)
Confirmed virologic rebound at W48, N
ATV/r + TDF/FTC
ATV/r + RAL N 1 9
Tested isolates 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
ATV/r + RAL
ATV/r + TDF/FTC
100
94.6
80.6 20 40 60 80 %
W24
(primary endpoint)
W48
86.5
69.4
* 1 patient with both PI and INSTI mutations
Virologic rebound
2 consecutive on-treatment HIV RNA > 40 c/mL
Last on-treatment HIV RNA > 40 c/mL followed by discontinuation
HARNESS
Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19, Van Lunzen J. JAIDS 2016;71:538-43

5. Kaplan-Meier estimate
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 %
ATV/r + RAL
ATV/r + TDF/FTC
B/L 4 8 12 16 20 24 28 32 36 40 44 48 52 60 80
100 72 37 68 67 35 64 57 54 34 39 25
Number of patients at risk
Week
HARNESS
Van Lunzen J. JAIDS 2016;71:538-43

6. HARNESS Study: switch to ATV/r + RAL
Safety at W48, N
ATV/r + TDF/FTC
N = 37
ATV/r + RAL
N = 72
Grade 3-4 AEs 5 13
Grade 2-4 drug-related AEs
Grade 3-4 total bilirubin 8 3 12
Renal toxicity 6 1
Discontinuation due to AE 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

7. 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