Efficacy of maraviroc (MVC) administered once-daily or twice-daily with boosted protease inhibitors to treatment-experienced patients S Taylor, 1 J Arribas, 2 C-F Perno, 3 R Burnside, 4 L McFadyen, 5 D Hardy, 6 H-J Stellbrink, 7 DA Cooper, 8 J-M Molina, 9 E van der Ryst, 5 J Heera, 4 H Valdez 10 1 Birmingham Heartlands Hospital, Birmingham, UK; 2 Hospital La Paz, Madrid, Spain; 3 University of Rome, Tor Vergata, Italy; 4 Pfizer Inc., Groton, CT, USA; 5 Pfizer Global Research and Development, Sandwich, Kent, UK; 6 Cedars-Sinai Medical Center/Geffen School of Medicine-UCLA, Los Angeles, CA, USA; 7 ICH Study Center, Hamburg, Germany; 8 University of New South Wales and St Vincent’s Hospital, Sydney, Australia; 9 Assistance Publique-Hopitaux de Paris, Paris, France; 10 Pfizer Inc., New York, NY, USA

Percentage of patients with HIV-1 RNA <50 copies/mL in the MOTIVATE studies through 48 weeks Hardy et al, Abstract 792, CROI, Patients (%) % 43.2%* 45.5%* *P < vs placebo Time (weeks) Placebo + OBT (N=209) MVC QD + OBT (N=414 ) MVC BID + OBT (N=426 ) Option to switch to open-label MVC BID In this analysis, non-completers and missing data were categorized as failures OBT, optimized background therapy

MOTIVATE: Effect of boosted PIs on MVC Cavg 1 Weatherly et al, Poster 17a, IWCPHIV, Kakuda et al, Antimicrob Agents Chemother, 2011; 55(5) Phase 2b/3 MVC 150 mg QD vs Phase 2a 300 mg BID monotherapy 1 Horizontal line = median Phase 2a 300 mg BID in asymptomatic HIV-1 infected subjects as target exposure (133 ng/mL) DRV/r boosts MVC exposures comparable to LPV/r and ATV/r in formal drug interaction studies in healthy volunteers MVC C avg (ng/mL) FPV/r QD n = Median = ATV/r QD IDV/r QD LPV/r QD SQV/r QD

Rationale for once-daily MVC with a boosted PI in treatment-experienced patients MVC monotherapy data show comparable antiviral responses with both 300 mg QD and BID 1 MVC 150 mg QD with boosted PIs achieved similar or greater concentrations compared to 300 mg BID without inhibitors/inducers 2 MVC when dosed QD with select boosted PIs may offer treating physicians and patients the option of simplified dosing of MVC 1. Fätkenheuer et al, Nat Med, Weatherley et al, Poster 17a, IWCPHIV, 2008.

Objective To determine in a post-hoc analysis, whether the efficacy of QD MVC in combination with select boosted PIs (excluding TPV/r and FPV/r) is comparable to MVC BID at week 48

Analysis population MOTIVATE patients n=1049 CCR5 + patients by enhanced sensitivity Trofile assay (ESTA) n=841 Boosted PI patients n=448 MVC QD n=187 MVC BID n=176 Placebo n=85 Boosted PI patients: patients whose baseline regimen included ATV/r, IDV/r, LPV/r, or SQV/r FPV/r patients n=149 MVC QD n=50 MVC BID n=56 Placebo n=43 Remainder patients n=244 ( TPV/r, unboosted or no PI) MVC QD n=98 MVC BID n=96 Placebo n=50

Baseline characteristics BID, twice daily; bPI, boosted PI; ESTA, enhanced sensitivity Trofile assay; MVC, maraviroc; QD, once daily

In a post-hoc analysis, a comparable percentage of patients treated with MVC QD or BID with a boosted PI achieved VL <50 copies/mL at Week 48 Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) n/N=85/18784/17614/ Difference (97.5% CI) QD vs PBO 27.8% (16.2, 39.4) BID vs PBO 30.6% (18.5, 42.7) BID, twice daily; CI, confidence interval; MVC, maraviroc; PBO, placebo; QD, once daily; VL, viral blood Placebo MVC 150 mg QD MVC 150 mg BID

Patient subgroup analyses: Screening VL < or ≥ 100,000 copies/mL Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) Placebo MVC 150 mg QD MVC 150 mg BID BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily; VL, viral blood Baseline HIV-1 RNA <100,000 copies/mL n/N=64/10558/9610/4230/7830/776/42 ≥100,000 copies/mL

Patient subgroup analyses: Baseline CD4 cell count < or ≥ 50 cells/mm 3 Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) Placebo MVC 150 mg QD MVC 150 mg BID Baseline CD4 count <50 cells/mm 3 n/N=5/295/271/2089/15483/14614/63 ≥50 cells/mm 3 BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily

Patient subgroup analyses: Number of active drugs in background regimen at baseline (wOBTss < or ≥ 1) Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) Placebo MVC 150 mg QD MVC 150 mg BID wOBTss <1 n/N=23/6420/561/2771/11968/11715/57 ≥1 BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily; wOBTss, weighed optimized background therapy susceptibility score

Patient subgroup analyses: First-time use of a selected boosted PI Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) Placebo MVC 150 mg QD MVC 150 mg BID 56.3 All boosted PI first use n/N=49/838/39 BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily Atazanavir/r first use Lopinavir/r first use /7119/324/1816/2820/292/1218/31

Patient subgroup analyses: Use of a selected boosted PI to which virus is susceptible Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) Placebo MVC 150 mg QD MVC 150 mg BID 56.5 All boosted PI susceptible n/N=36/619/29 BID, twice daily; MVC, maraviroc; PBO, placebo; QD, once daily Atazanavir susceptible Lopinavir susceptible /6214/243/1313/2019/305/1521/38

Conclusions Comparable efficacy was demonstrated in subjects treated with MVC 150 mg QD or BID compared to placebo in combination with a boosted PI (except TPV/r and FPV/r) Efficacy was maintained with MVC QD or BID with a boosted PI compared to placebo in patients: –with high screening VL or low baseline CD4+ cells –receiving >1 other fully active drug (wOBTss >1) –receiving selected boosted PI for the first time or with documented viral susceptibility to the selected boosted PI MVC administered QD in combination with select boosted PIs may be a potential option for treatment- experienced patients seeking a simplified treatment regimen

Acknowledgments Thank you to all study participants and investigators who participated in the MOTIVATE 1 and MOTIVATE 2 studies. Editorial support was provided by Dr Clemence Hindley at Complete Medical Communications and funded by ViiV Healthcare

BACK UPS

Maraviroc 150 mg QD + Darunavir/r 800/100 mg QD Ongoing study evaluating intensive PK in HIV-infected patients receiving MVC 150 mg QD + DRV/r 800/100 mg QD MVC 150 mg QD + DRV/r (n=15) MVC 300 mg BID + TDF/FTC (n=12) MVC trough Median50 ng/mL48 ng/mL Mean65 ng/mL48 ng/mL Taylor et al, CROI, 2011

In a post-hoc analysis a comparable percentage of patients on MVC QD or BID with a boosted PI achieved a VL <50 copies/mL at Week 48 Patients with HIV-1 RNA <50 copies/mL at Week 48 (%) n/N=85/18784/17614/ Difference (97.5% CI) QD vs PBO 27.8% (16.2, 39.4) BID vs PBO 30.6% (18.5, 42.7) Difference (95% CI) QD vs BID -2.4% (-12.5, 7.7) Placebo MVC 150 mg QD MVC 150 mg BID BID, twice daily; CI, confidence interval; MVC, maraviroc; PBO, placebo; QD, once daily; VL, viral blood