1. Comparison of EFV vs MVC
ARV-trial.com
Comparison of EFV vs MVC
MERIT Study 1

2. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
ARV-trial.com
MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
Design
Randomisation*
1 : 1
Open-label
W48
W96
> 16 years
ARV-naïve
HIV RNA > 2,000 c/mL
Any CD4 cell count
R5 HIV-1 infection (original Trofile assay)
No resistance to
EFV, ZDV or 3TC
N = 360
MVC 300 mg BID * + ZDV/3TC BID
N = 361
EFV 600 mg QD + ZDV/3TC BID
*Randomisation was stratified by screening
HIV RNA (< or > 100,000 c/mL) and geographic location
(Northern or Southern Hemisphere)
Objective
Non inferiority of MVC vs EFV: % HIV RNA < 400 c/mL and < 50 c/mL (co-primary endpoints) at W48, by ITT analysis (lower margin of the 1-sided 97.5% CI for the difference = - 10%) [missing values were classified as non responses]
* A third arm with MVC 300 mg QD was discontinued for lack of efficacy at W16
MERIT
Cooper DA. JID 2010;201:803-13 2

3. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
ARV-trial.com
MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
Baseline characteristics and patient disposition
MVC N = 360
EFV N = 361
Mean age, years
36.7
37.4
Female
29%
28%
White/Black/Other
57% / 34% / 9%
55% / 37% / 8%
HIV RNA (log10 c/mL), mean
4.86
4.88
CD4 cell count (/mm3), median
241
254
Discontinuation by W48
97 (26.9%)
91 (25.2%)
For lack of efficacy 43 15
For adverse event 49
78% of black and 72% of female patients were in the Southern Hemisphere
Screening HIV RNA > 100,000 c/mL: 45% in the Southern Hemisphere vs 38% in the Northern Hemisphere
MERIT
Cooper DA. JID 2010;201:803-13 3

4. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
ARV-trial.com
MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
Response to treatment at week 48 (ITT)
MVC (N = 360)
EFV (N = 361) %
HIV RNA < 400 c/mL
HIV RNA < 50 c/mL
HIV RNA < 50 c/mL
100 80
70.6
73.1
69.3
69.6
71.6
65.3
66.0
59.6 60 40 20
N =
204
211
156
150
All patients
Baseline HIV RNA
Lower margin of the 97.5% CI for the difference = - 9.5
Lower margin of the 97.5% CI for the difference =
 MVC not non inferior to EFV
< 100,000 c/mL
> 100,000 c/mL
Mean CD4/mm3 increase at W48 (LOCF): 170 (MVC) vs 144 (EFV) (p = 0.008)
MERIT
Cooper DA. JID 2010;201:803-13 4

5. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
ARV-trial.com
MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
Post hoc reanalysis A descriptive post hoc reanalysis was done for patients whose screening samples retrospectively retested as R5 by the current Trofile assay. The enhanced version of this assay has greater sensitivity for detecting minority CXCR4-using strains than the original Trofile assay. This led to exclude 107 of the 721 original patients
Baseline characteristics and patient disposition (Post hoc reanalysis)
Post hoc reanalysis
MVC N = 311
EFV N = 303
Mean age, years
36.4
37.3
Female
29%
30%
HIV RNA (log10 c/mL), mean
4.88
4.85
CD4 cell count (/mm3), median
236
254
Discontinuation by W48
76 (24.4%)
78 (25.7%)
For lack of efficacy 29 12
For adverse event 13 43
MERIT
Cooper DA. JID 2010;201:803-13 5

6. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
ARV-trial.com
MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
Response to treatment at week 48 (ITT): post hoc reanalysis
(exclusion of patients with non-R5 virus at screening by the enhanced Trofile assay)
MVC (N = 311)
EFV (N = 303) %
HIV RNA < 400 c/mL
HIV RNA < 50 c/mL
HIV RNA < 50 c/mL
100 80
73.3
72.3
71.8
72.1
68.5
68.3
64.2
62.5 60 40 20
N =
177
183
134
120
All patients
Baseline HIV RNA
Lower margin of the 97.5% CI for the difference = - 6.4
Lower margin of the 97.5% CI for the difference = - 7.4
< 100,000 c/mL
> 100,000 c/mL
Difference in mean CD4/mm3 increase at W48 (LOCF) MVC minus EFV = (p = 0.004)
MERIT
Cooper DA. JID 2010;201:803-13 6

7. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
ARV-trial.com
MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
Safety (Original patient population)
Resistance (Post hoc reanalysis)
Virologic failure by the TLOVR algorithm (HIV RNA > 50 c/mL):29 MVC vs 13 EFV
MVC failures, N = 29
Emergence of CXCR4-using virus, N = 9
Emergence of R5 resistant to MVC, N = 4
R5 virus without any resistance, N = 11
Resistance to 3TC only, N = 5
EFV failures, N = 13
Emergence of resistance to EFV, N = 9
Resistance to 3TC only, N = 1
No resistance, N = 3
MVC
EFV
Serious adverse event
11.3%
12.7%
Discontinuation for adverse event
15 (4.2%)
49 (13.6%)*
Category C events
1.7%
3.3%
Malignancies
0.6%
1.9%
AST elevation Grade 3 (5-10 x ULN) Grade 4 (> 10 x ULN)
7 (2.0%) 5 (1.4%)
11 (3.1%) 2 (0.6%)
ALT elevation Grade 3 (5-10 x ULN)
Grade 4 (> 10 x ULN)
9 (2.5%) 2 (0.6%)
* p < 0.001
MERIT
Cooper DA. JID 2010;201:803-13 7

8. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
ARV-trial.com
MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC
Discussion - Conclusion
MVC was not non inferior to EFV, when combined with ZDV/3TC
Increase in CD4 count was significantly greater for MVC than for EFV
There were more discontinuations for lack of efficacy in the MVC group
When the screening samples were retested with the more sensitive Trofile assay, 15% of patients were found to have CXCR4 virus at screening
In the post hoc reanalysis, excluding these patients
MVC was non inferior to EFV, for proportion of HIV RNA < 50 c/mL at W48
Virologic response rates were similar between MVC and EFV within each viral load stratum (HIV RNA < or > 100,000 c/mL)
Response rate was higher for MVC in patients from Northern Hemisphere due to higher adverse event-related discontinuations for EFV
Response rate was lower for MVC in patients from Southern Hemisphere, this result being driven by more black patients receiving MVC than EFV defaulting
MVC was associated with significantly fewer adverse event-related discontinuations than EFV and with fewer malignancies and category C events
There were no difference between groups in the incidence of elevation in transaminases, and there were no unexpected safety findings
MERIT
Cooper DA. JID 2010;201:803-13 8