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

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

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

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 = - 10.9  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

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

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 = + 30 (p = 0.004) MERIT Cooper DA. JID 2010;201:803-13 6

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

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