1. Switch to DRV/r monotherapy
ARV-trial.com
Switch to DRV/r monotherapy
MONOI
MONET
PROTEA 1

2. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Design
Randomisation*
1 : 1
Open-label
W48
W144
N = 129
293 HIV+ adults
On 2 NRTIs + (PI or NNRTI)
Darunavir-naïve
No history of prior virologic failure
HIV-1 RNA < 50 c/mL > 6 months
DRV/r 800/100 mg qd
+ 2 NRTIs (optimisation at D0**)
N = 127
DRV/r 800/100 mg qd
* Randomisation was stratified on the use of PI or NNRTI
(57% patients on PI, 43% on NNRTI)
** NRTI used at baseline: TDF + FTC = 46% ; ABC + 3TC: 31% ;
ZDV + 3TC = 10% ; TDF + 3TC = 7% ; other combinations: 6%
Objective
Non inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL at W48 (per-protocol analysis, switch= failure, TLOVR algorithm) ; lower limit of the 95% CI for the difference= - 12%, 80% power
MONET
Arribas J, AIDS 2010;24:

3. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
ARV-trial.com
MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Baseline characteristics and patient disposition
DRV/r qd
+ 2 NRTIs
DRV/r qd monotherapy
Mean age, years 44 43
Female
17%
22%
IV drug user 9%
16%
HCV antibody positive
CD4 cell count, mean/mm3
579
571
Duration of ARV treatment, years
5.9
7.4
PI treatment at screening
57%
56%
NNRTI treatment at screening
43%
44%
Protease inhibitor naïve at screening
28%
23%
Protocol defined treatment failure at W48, n (%)
19 (15%)
20 (16%)
Discontinuation for adverse event 4
Confirmed HIV RNA elevation 7 11
At baseline, 13 patients had HIV-1 RNA levels > 50 c/mL (9 in the monotherapy arm and 4 in the triple therapy arm) despite having results < 50 c/ml at screening
MONET
Arribas J, AIDS 2010;24:

4. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Results: W48 outcome 25 50
100 75
87.8%
84.3%
123 %
85.3%
129
127
86.2%
Per-protocol
(primary endpoint)
ITT N=
HIV-1 RNA < 50 c/mL (TLOVR, switch = failure)
95% CI for the difference = ; 6.8
95% CI for the difference = ; 8.8
95% CI for the difference = ; 4.2
93.5%
95.1%
ITT, switch-included
analysis
DRV/r + 2 NRTIs
DRV/r qd monotherapy
Non inferiority of DRV/r monotherapy
MONET
Arribas J, AIDS 2010;24:

5. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Outcomes of confirmed HIV RNA elevations
Patient
HIV RNA values (c/mL)
Change in Treatment
Last HIV RNA (c/mL)
DRV/r monotherapy arm 1
140 ; 133
None
< 50 2
59 ; 214
ZDV/3TC + NVP 3
132 ; 139
LPV/r monotherapy 4
539 ; 862
TDF/FTC/EFV 5
67 ; 810
810 6
; 628 7
158 ; 140
ABC/3TC + DRV/r 8
51 ; 80 9
106 ; 268
TDF/FTC + DRV/r 10
722 ; 157 11
779 ; 267
Triple therapy arm (DRV/r + 2 NRTIs)
294 ; 116
; 3.400
78 ; 50
164 ; 67
989 ; 59
746 ; 2.230
2.230
128 ; 548
MONET
Arribas J, AIDS 2010;24:

6. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Outcomes of discontinuations from the trial
Patient
Reason for discontinuation
Change in Treatment
Last HIV RNA (c/mL)
DRV/r monotherapy arm 12
History of virologic failure
ABC/3TC + ATV/r
< 50 13
Adverse event
TDF + 3TC + EFV 14
Investigator decision
TDF/FTC + LPV/r 15
ABC/3TC + NVP 16 17
Withdrew consent
ZDV/3TC + EFV 18
None 19
Off all ARVs
> 20
In prison 8
TDF/FTC + NVP 9
ZDV/3TC + NVP
Triple therapy arm (DRV/r + 2 NRTIs) 10
Pregnancy 11
NZDV/3TC + NVP
Private reasons
TDF + ZDV + 3TC
ZDV/3TC + LPV/r
RNA > 50 c/mL at SCR + BL
No data
Switched to DRV/r
DRV/r monotherapy
MONET
Arribas J, AIDS 2010;24:

7. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Other endpoints
In multivariate analysis, hepatitis C co-infection was a significant predictor of confirmed HIV RNA elevations (p < 0.01)
Resistance data: Genotype was available for 35/61 patients with HIV RNA > 50 c/mL (22 in the monotherapy group and 13 in the triple therapy group)
Resistance mutations to PI in 1 one patient in each arm, with no phenotypic resistance to DRV. HIV-1 RNA returned to < 50 c/mL without changing therapy in both patients
Most common grade 2 to 4 adverse events (AE) were gastrointestinal
Serious AE were seen in 9 patients in each group
Discontinuation for AE by W48 occurred in 8 patients in the monotherapy group and 3 in the triple therapy group
Grade 1 to 4 nervous system AE were seen in 16% of patients in each group, and Grade 1 to 4 psychiatric AE in 9% of patients in each group
There were more haematological abnormalities in the triple therapy arm, related to zidovudine
MONET
Arribas J, AIDS 2010;24:

8. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Conclusions from W48 data
In patients with virologic suppression on standard triple therapy (2 NRTIs + 1 NNRTI or 1 PI), once-daily DRV/r monotherapy has shown non inferior HIV RNA suppression at week 48 compared with a standard therapy of 2 NRTIs + once-daily DRV/r
A switch to once-daily DRV/r monotherapy can be considered in patients who have HIV RNA < 50 c/mL for more than 6 months on other treatments and no history of virologic failure, but wish to avoid toxicities related to other ARVs
MONET
Arribas J, AIDS 2010;24:

9. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
Results: W96 outcome
HIV-1 RNA < 50 c/mL at W96,
ITT, TLOVR (%)
Monotherapy is not noninferior with switch = failure analysis at W96
Δ -5.8% (95% CI: -16.0% to +4.4%)
If resuppression with intensification included as success, then monotherapy is noninferior at W96
Δ +1.4% (95% CI: -5.5% to +8.3%) 40
100 20 80 60
DRV/r monotherapy (N = 127)
DRV/r + 2 NRTIs (N = 129)
80.6
74.8
Switch = failure
92.1
90.7
Switch allowed
MONET
Rieger A, et al. AIDS Abs. THLBB209

10. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy
HIV-1 RNA < 50 c/mL at W144 (ITT-TLOVR)
Switch* = failure
Switch* included
2 consecutive HIV-1 RNA > 50 c/mL:
DRV/r monotherapy, N = 21
DRV/r + 2 NRTI, N = 13
18/21 and 10/13 had HIV-1 RNA < 50 c/mL at W144
Level of HIV-1 RNA at baseline and HCV co-infection were significantly associated with transient viremia during the 144 weeks (p < 0.05)
Resistance emergence to PI (IAS-USA): 1 in each arm, both before W24
Lower margin of the 95 % CI of the  %
- 8.7 % 25 50
100 75
75 %
84 %
DRV/r +
2 NRTI %
83.5 %
DRV/r mono
69 %
Non inferiority of DRV/r monotherapy
only in the « switch-included » analysis
* Change in ARV
MONET
Arribas JR, HIV Medicine 2012;13: