PROBE Study PROBE Study switch to DRVr RPV Design Age 18 years HIV No previous resistance to study drugs HIV1 RNA lt 50 cml 6 months On stable 6 months PIr 2 NRTI TDFFTC or ABC3TC ID: 554916
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Slide1
Switch to DRV/r + RPV
PROBE
StudySlide2
PROBE Study: switch to DRV/r + RPV
Design
Age ≥ 18 years
HIV+
No previous resistance to study drugsHIV-1 RNA < 50 c/ml ≥ 6 monthsOn stable (≥ 6 months) PI/r + 2 NRTI (TDF/FTC or ABC/3TC)HBs antigen negative
DRV/r 800/100 mg + RPV 25 mg qd
Continuation of triple therapy
118
N = 30
N = 30
Randomisation
1: 1Open-label
W48
Objective
Primary endpoint: proportion with HIV RNA < 50 c/mL at W24 and W48 (ITT, FDA snapshot) with non inferiority of DRV/r + RPV (lower limit
of the 95% CI for the difference = -12%, 80% power)
Protocol-defined
virologic
failure: 2 consecutive HIV RNA > 50 c/mL
Maggiolo
F. JAIDS 2016;72:46-51
PROBESlide3
Baseline characteristics (mean)
DRV/r + RPV
N = 30
PI/r + 2 NRTI
N = 30
Age, years
49
48
Female
30%
10%
cART
, %
TDF/FTC / ABC/3TC
DRV/r / ATV/r
NA
90 / 10
43 / 57
Current CD4/mm
3
615
631
Pre-ART CD4/mm
3233263Pre-ART HIV RNA, copies/mL272,000215,000Duration of current ART, months4938Duration of HIV RNA < 50 c/mL, months5759Baseline HIV DNA, copies/106 cells, median15,20010,900
Maggiolo F. JAIDS 2016;72:46-51
PROBE
PROBE Study: switch to DRV/r + RPV Slide4
Virologic
n
on inferiority at W24 and W48
118
100
80
60
40
20
0
W
24
W
48
W
24
W
48
W
24
W
48
HIV RNA
< 50 c/ml
HIV RNA > 50 c/ml
N
o data in
window
%
100
7*
90.1
0
3
0
96.7
93.4
3
3
3**
0
Virologic
outcome
at
W24 and W48 (ITT,
snapshot
)
DRV/r + RPV (N = 30)
PI/r + 2 NRTI (N = 30)
Favors
Triple
ART
DRV/r + RPV
W
24
W
48
-0.7
+20.7
+13.5
-7.5
-12
+12
Difference (95% CI)
* blips at 57 and 138 c/mL
** blip at 59 c/mL
Maggiolo
F. JAIDS 2016;72:46-51
PROBE
PROBE Study: switch to DRV/r + RPV Slide5
DRV/r + RPV
PI/r + 2 NRTI
Severe adverse
event
s, n
0
0
Discontinuation for adverse event, n
0
0
Grade 3-4 laboratory abnormalities, n
0
0
Mean value of laboratory parameter
Baseline
W48
Baseline
W48
Total cholesterol, mg/
dL
183
200
184
188HDL-cholesterol, mg/dL47494545Triglycerides, mg/dL200173128143eGFR, mL/min1011009995Bone mineral density
-
- 0.0003
-
- 0.014
Safety and Tolerability at W48
DRV/r + RPV
PI/r + 2 NRTI
Mean change in CD4/mm
3
from baseline
+ 15
+ 16
Mean change in CD8/mm
3
from baseline
-
21
-
41
Mean CD8+38+HLADR+ cell count at W48
3.4%*
5.2%*
Secondary endpoints at W48
* p = 0.018
Maggiolo
F. JAIDS 2016;72:46-51
PROBE
PROBE Study: switch to DRV/r + RPV Slide6
PROBE Study: switch to DRV/r + RPV
Conclusion
A
rilpivirine
plus ritonavir-boosted DRV dual therapy was not inferior over 48 weeks to a standard boosted PI–based triple cARTThe dual therapy did not negatively affect lipid profile and renal function and was more friendly on bone mineral densityThis approach constitutes an alternative for patients experiencing nucleoside reverse transcriptase inhibitor–related toxicitiesLimitationsSmall sample sizeMaggiolo F. JAIDS 2016;72:46-51
PROBE