1. Switch to LPV/r monotherapy
ARV-trial.com
Switch to LPV/r monotherapy
Pilot LPV/r
M03-613
LPV/r Mono
KalMo OK
OK04
KALESOLO
MOST
HIV-NAT 077 1

2. MOST Study: Switch to LPV/r monotherapy
Design
Randomisation
1 : 1
Open-label
W96
N = 31
Target of 100 HIV+
On cART > 6 months
HIV-1 RNA < 50 c/mL > 3 months
Baseline determination of HIV-1 RNA in CSF and genital secretions
Continuation current antiretroviral therapy (cART)*
N = 29
LPV/r 400/100 mg bid
* Possibility offered to switch to LPV/r monotherapy at W48 delayed switch)
Objective
Non inferiority of the monotherapy group in the proportion of patients with HIV-1 RNA < 50 c/mL in the plasma and treatment failure in the CNS or the genital compartment without modification of treatment (per-protocol analysis) ; lower limit of CI for the difference = - 12%, 80% power
Study was prematurely stopped before full recruitment when 6 patients on monotherapy (none in cART group) demonstrated a virologic failure in blood
MOST
Gutmann C, AIDS 2010;24:

3. MOST Study: Switch to LPV/r monotherapy
ARV-trial.com
MOST Study: Switch to LPV/r monotherapy
Baseline characteristics
Continuation of cART
N = 31
LPV/r monotherapy
N = 29
Mean age, years 46 42
Female
23%
34%
CDC stage C
CD4 cell count at baseline, median/mm3
465
498
CD4 cell count at nadir, median/mm3
160
HIV-RNA set point, mean log10 c/ml
4.7
4.9
ARV at inclusion
PI-based
74%
73%
NNRTI-based
24%
3 NRTIs 3%
MOST
Gutmann C, AIDS 2010;24:

4. MOST Study: Switch to LPV/r monotherapy
Outcome
Median follow-up: 48 weeks
Virologic failure (2 consecutive plasma HIV-1 RNA > 400 c/mL) occurred in 6/29 patients in the LPV/r monotherapy group, after a median of 12 weeks, vs 0/31 in the continued antiretroviral therapy group
In these 6 failures, the median duration of HIV-1 RNA < 50 c/mL was 50 months ; 5/6 patients had clinical symptoms at the time of failure, all symptoms resolving after treatment switch ; all 6 patients had a nadir CD4 cell count < 200/mm3
CSF was examined in 45 patients at study termination (25 on LPV/r monotherapy and plasma HIV-1 RNA < 400 c/mL, 5 failing monotherapy and 15 continuing prior ARV therapy with plasma HIV-1 RNA < 50 c/mL)
CSF HIV-1 RNA was > 40 c/mL
8/25 patients on monotherapy
none of the 15 patients still on continued treatment (p = 0.01)
No marked elevation of HIV-1 RNA in the genital secretions
MOST
Gutmann C, AIDS 2010;24:

5. MOST Study: Switch to LPV/r monotherapy
Patients with treatment failure in blood or detection of elevated HIV-1 RNA in CSF
Sex
Pre-Treatment
CD4 nadir /mm3
Treatment arm
Week on study/on monotherapy
HIV-1 RNA
plasma, log10 c/ml
CSF,
log10 c/mL
Blood failure (HIV-1 RNA > 400 c/mL) 1
Male
TDF/FTC/ATV/r 57
LPV/r mono 12
4.3
5.1 2
Female
ZDV/3TC/LPV/r 5
Delayed Switch
60/12
4.2
3.1 3
ABC/3TC/LPV/r
149
4.1
5.0 4
ZDV/3TC/EFV 7 24
3.0
TDF/3TC/LPV/r 54 6 ND
TDF/3TC/EFV
160
3.7
HIV-RNA detectable in CSF
Monotherapy arm
TDF/FTC/LPV/r
211
96/48
< 1.6
2.9
TDF/3TC/ATV/r
370
66/18
2.2
3.4
100 63
2.3
TDF/3TC/ZDV/EFV
130
68/20
2.1
120
72/24 20 37
2.4
ABC/3TC/ZDV/LPV/r
220 48
1.9
2.5 8 17 44
HIV-RNA detectable in CSF Continuation therapy arm 9
cART at baseline
1.6 10
126
1.7 11
185
48/0
MOST
Gutmann C, AIDS 2010;24:

6. MOST Study: Switch to LPV/r monotherapy
Conclusions
Maintenance of HIV treatment with LPV/r monotherapy should not be recommended as a standard strategy ; this is particularly evident in patients with a CD4 cell count < 200/mm3 at nadir
The proportion of patients with detectable HIV-1 RNA in CSF was not only significantly higher on LPV/r monotherapy than on continued combination therapy (32% vs 0% ; p = 0.01), but the difference appears biologically (CSF inflammation) and clinically (acute symptoms) relevant
MOST
Gutmann C, AIDS 2010;24: