1. ARV-trial.com
Switch to DRV/r + RPV
PROBE Study 1

2. PROBE Study: switch to DRV/r + RPV
118
Randomisation
1: 1
Open-label
W48
Design
Age ≥ 18 years
HIV+
No previous resistance to study drugs
HIV-1 RNA < 50 c/ml ≥ 6 months
On stable (≥ 6 months) PI/r + 2 NRTI (TDF/FTC or ABC/3TC)
HBs antigen negative
N = 30
DRV/r 800/100 mg + RPV 25 mg qd
Continuation of triple therapy
N = 30
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
PROBE
Maggiolo F. JAIDS 2016;72:46-51

3. PROBE Study: switch to DRV/r + RPV
Baseline characteristics (mean)
DRV/r + RPV
N = 30
PI/r + 2 NRTI
Age, years 49 48
Female
30%
10%
cART, %
TDF/FTC / ABC/3TC
DRV/r / ATV/r NA
90 / 10
43 / 57
Current CD4/mm3
615
631
Pre-ART CD4/mm3
233
263
Pre-ART HIV RNA, copies/mL
272,000
215,000
Duration of current ART, months 38
Duration of HIV RNA < 50 c/mL, months 57 59
Baseline HIV DNA, copies/106 cells, median
15,200
10,900
PROBE
Maggiolo F. JAIDS 2016;72:46-51

4. PROBE Study: switch to DRV/r + RPV
118
Virologic outcome at W24 and W48 (ITT, snapshot)
DRV/r + RPV (N = 30)
PI/r + 2 NRTI (N = 30)
100 80 60 40 20
W24
W48
HIV RNA < 50 c/ml
HIV RNA > 50 c/ml
No data in window % 7*
90.1 3
96.7
93.4
3**
Favors
Triple ART
DRV/r + RPV
W24
W48
-0.7
+20.7
+13.5
-7.5
-12
+12
Difference (95% CI)
Virologic non inferiority at W24 and W48
* blips at 57 and 138 c/mL
** blip at 59 c/mL
PROBE
Maggiolo F. JAIDS 2016;72:46-51

5. PROBE Study: switch to DRV/r + RPV
Secondary endpoints at W48
DRV/r + RPV
PI/r + 2 NRTI
Mean change in CD4/mm3 from baseline
+ 15
+ 16
Mean change in CD8/mm3 from baseline
- 21
- 41
Mean CD8+38+HLADR+ cell count at W48
3.4%*
5.2%*
* p = 0.018
Safety and Tolerability at W48
DRV/r + RPV
PI/r + 2 NRTI
Severe adverse events, n
Discontinuation for adverse event, n
Grade 3-4 laboratory abnormalities, n
Mean value of laboratory parameter
Baseline
W48
Total cholesterol, mg/dL
183
200
184
188
HDL-cholesterol, mg/dL 47 49 45
Triglycerides, mg/dL
173
128
143
eGFR, mL/min
101
100 99 95
Bone mineral density -
PROBE
Maggiolo F. JAIDS 2016;72:46-51

6. 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 cART
The dual therapy did not negatively affect lipid profile and renal function and was more friendly on bone mineral density
This approach constitutes an alternative for patients experiencing nucleoside reverse transcriptase inhibitor–related toxicities
Limitations
Small sample size
PROBE
Maggiolo F. JAIDS 2016;72:46-51