1. Comparison of EFV vs MVC  MERIT Study

2.  Design N = 361 N = 360  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] MVC 300 mg BID * + ZDV/3TC BID EFV 600 mg QD + ZDV/3TC BID > 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 *Randomisation was stratified by screening HIV RNA ( 100,000 c/mL) and geographic location (Northern or Southern Hemisphere) Cooper DA. JID 2010;201:803-13 MERIT * A third arm with MVC 300 mg QD was discontinued for lack of efficacy at W16 MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC Randomisation* 1 : 1 Open-label W48W96

3. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC MVC N = 360 EFV N = 361 Mean age, years36.737.4 Female29%28% White/Black/Other57% / 34% / 9%55% / 37% / 8% HIV RNA (log 10 c/mL), mean4.864.88 CD4 cell count (/mm 3 ), median241254 Discontinuation by W4897 (26.9%)91 (25.2%) For lack of efficacy4315 For adverse event1549 Baseline characteristics and patient disposition 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

4. Response to treatment at week 48 (ITT) Mean CD4/mm 3 increase at W48 (LOCF): 170 (MVC) vs 144 (EFV) (p = 0.008) MERIT MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC MVC (N = 360) EFV (N = 361) All patients % 70.6 65.3 69.6 73.1 69.3 71.6 0 20 40 60 80 100 HIV RNA < 400 c/mL HIV RNA < 50 c/mL 59.6 66.0 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 N =204211156150 Baseline HIV RNA < 100,000 c/mL > 100,000 c/mL Cooper DA. JID 2010;201:803-13

5. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC Post hoc reanalysis MVC N = 311 EFV N = 303 Mean age, years36.437.3 Female29%30% HIV RNA (log 10 c/mL), mean4.884.85 CD4 cell count (/mm 3 ), median236254 Discontinuation by W4876 (24.4%)78 (25.7%) For lack of efficacy2912 For adverse event1343 Baseline characteristics and patient disposition (Post hoc reanalysis)  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 MERIT Cooper DA. JID 2010;201:803-13

6. Response to treatment at week 48 (ITT): post hoc reanalysis (exclusion of patients with non-R5 virus at screening by the enhanced Trofile assay) Difference in mean CD4/mm 3 increase at W48 (LOCF) MVC minus EFV = + 30 (p = 0.004) MERIT MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC HIV RNA < 400 c/mL % 73.3 68.5 71.8 72.3 68.3 72.1 0 20 40 60 80 100 64.2 62.5 Lower margin of the 97.5% CI for the difference = - 6.4 Lower margin of the 97.5% CI for the difference = - 7.4 MVC (N = 311) EFV (N = 303) HIV RNA < 50 c/mL All patients Baseline HIV RNA < 100,000 c/mL> 100,000 c/mL N =177183134120 Cooper DA. JID 2010;201:803-13

7. MERIT Study: maraviroc vs efavirenz, in combination with ZDV/3TC  Safety (Original patient population) MVCEFV Serious adverse event11.3%12.7% Discontinuation for adverse event 15 (4.2%) 49 (13.6%)* Category C events1.7%3.3% Malignancies0.6%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%) 11 (3.1%) 2 (0.6%) * p < 0.001 –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  Resistance (Post hoc reanalysis) MERIT Cooper DA. JID 2010;201:803-13

8. 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 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