1. 48-week results of once-daily maraviroc (MVC) 150 mg in combination with ritonavir-boosted atazanavir (ATV/r) compared to emtricitabine/tenofovir (FTC/TDF) + ATV/r in treatment-naïve patients infected with R5 HIV-1 (Study A4001078) Simon Portsmouth, 1 Charles Craig, 2 Anthony Mills, 3 Donna Mildvan, 4 Daniel Podzamczer, 5 Gerd Fätkenheuer, 6 Manuel Leal, 7 Hernan Valdez, 1 Srinivas Rao Valluri, 1 Jayvant Heera 1 1 Pfizer Inc., New York, NY, USA; 2 Pfizer, Sandwich, Kent, UK; 3 Anthony Mills MD, Los Angeles, CA, USA; 4 Beth Israel Medical Center Division of Infectious Diseases, New York, NY, USA; 5 HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, Barcelona, Spain; 6 University Hospital of Cologne Köln, Germany; 7 Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Infectious Disease Service, Virgen del Rocio University Hospital, Seville, Spain

2. Rationale for MVC + boosted PI regimen Potential for early use: prevalence of CCR5 tropic virus is greatest in treatment-naïve individuals 1 Nucleoside-sparing regimen Good penetration of MVC in CSF and genital secretions 2-4 MOTIVATE and PK studies support use of MVC 150 mg QD with selected ritonavir-boosted PIs 1. Hoffmann, Eur J Med Res, 2007. 2. Tiraboschi et al, J Acquir Immune Defic Syndr, 2010 3. Dumond et al, J Acquir Immune Defic Syndr, 2009. 4. Brown et al, J Infect Dis, 2011 Study A4001078: an exploratory pilot study of a low pill burden QD dual-therapy regimen, MVC + ATV/r

3. Study design Open-label, 48-week Phase 2b pilot study Patient eligibility criteria – R5 HIV (ESTA) at screening – ≥16 years of age – HIV-1 RNA ≥1000 copies/mL – CD4 ≥100 cells/mm 3 – No evidence of resistance to ATV/r, TDF, or FTC – Study has iDMC – Ongoing study: USA, Spain, Germany – Extended to 96 weeks – Study is not powered to show a treatment difference and no formal comparative statistics will be performed Randomization 1:1 N=121 MVC (150 mg QD) + ATV/r (300/100 mg QD) FTC/TDF + ATV/r (300/100 mg QD) 024 wk 48 wk Screening (6 weeks) 16 wk Week 2 First 15 US patients Serial PK of MVC Interim analysesPrimary analysis *Sparse PK sampling on all patients at Weeks 2 (non-PK substudy), 12 and 24 (Vourvahis. Abstract 37 IWCPHIV, 2010)

4. VL, HIV-1 RNA, viral load Study disposition MVC + ATV/r n=60 FTC/TDF + ATV/r n=61 Discontinued n=7 2 AE (vomiting, jaundice) 3 lost to follow-up 1 withdrew consent 1 insufficient clinical response (VL 934 copies/mL) Enrolled into study n=121 Screening n=220 Discontinued n=7 2 lost to follow-up 1 withdrew consent 2 protocol violations 1 pregnancy 1 other: possible TDF-related kidney failure Continuing in study n=53 Continuing in study n=54 Two patients in each arm experienced protocol defined treatment failure

5. Summary of baseline characteristics MVC + ATV/r n=60 FTC/TDF + ATV/r n=61 Mean age, years (range)38.3 (21–61)35.3 (18–68) Male, n (%)56 (93.3)52 (85.2) Race, n (%) White Black Asian Other 45 (75.0) 13 (21.7) 0 2 (3.3) 46 (75.4) 11 (18.0) 3 (4.9) 1 (1.6) Median CD4 + count, cells/mm 3 (range) 344 (160–744) 358 (110–902) Mean HIV-1 RNA, log 10 copies/mL (range) 4.6 (3.4–5.9)4.7 (3.3–5.9) HIV-1 RNA ≥100,000 copies/mL, n (%) 16 (27)22 (36)

6. HIV-1 RNA <400 copies/mL at Week 48 Patients with HIV-1 RNA <400 copies/mL (%) MVC + ATV/r (N=59) FTC/TDF + ATV/r (N=61) 89.8% 86.9% Intent-to-treat. Missing=failure Study week

7. HIV-1 RNA <50 copies/mL at Week 48 Study week 83.6% 74.6% MVC + ATV/r (N=59) FTC/TDF + ATV/r (N=61) Intent-to-treat. Missing=failure Patients with HIV-1 RNA <50 copies/mL (%)

8. <100,000 copies/mL≥100,000 copies/mL Week 24Week 48Week 24Week 48 Baseline HIV-1 RNA Patients with HIV-1 RNA <50 copies/mL (%) 0 10 60 70 80 90 100 50 40 30 20 HIV-1 RNA <50 copies/mL at Week 24 and Week 48 according to baseline viral load 37/39 35/4313/16 17/22 81.4 94.9 81.3 77.3 Intent-to-treat. Missing=failure MVC + ATV/r FTC/TDF + ATV/r

9. HIV-1 RNA <50 copies/mL at Week 24 and Week 48 according to baseline viral load Week 24Week 48Week 24Week 48 Patients with HIV-1 RNA <50 copies/mL (%) 0 10 60 70 80 90 100 50 40 30 20 <100,000 copies/mL≥100,000 copies/mL Baseline HIV-1 RNA 34/39 33/43 17/22 11/16 76.7 87.2 68.8 77.3 37/39 35/4313/16 17/22 81.4 94.9 81.3 77.3 Intent-to-treat. Missing=failure MVC + ATV/r FTC/TDF + ATV/r

10. HIV-1 RNA <400 copies/mL at Week 24 and Week 48 according to baseline viral load Week 24Week 48Week 24Week 48 Patients with HIV-1 RNA <400 copies/mL (%) 0 10 60 70 80 90 100 50 40 30 20 <100,000 copies/mL≥100,000 copies/mL Baseline HIV-1 RNA 37/39 39/43 15/16 20/22 90.7 94.9 93.8 90.9 Intent-to-treat. Missing=failure MVC + ATV/r FTC/TDF + ATV/r

11. HIV-1 RNA <400 copies/mL at Week 24 and Week 48 according to baseline viral load Week 24Week 48Week 24Week 48 Patients with HIV-1 RNA <400 copies/mL (%) 0 10 60 70 80 90 100 50 40 30 20 <100,000 copies/mL≥100,000 copies/mL Baseline HIV-1 RNA 34/39 38/43 19/22 15/16 88.4 87.2 93.8 86.4 MVC + ATV/r FTC/TDF + ATV/r 37/39 39/43 15/16 20/22 90.7 94.9 93.8 90.9 Intent-to-treat. Missing=failure

12. Outcomes for all patients with VL >50 copies/mL at Week 48 a Patient discontinued at Week 84 due to insufficient clinical response b Patient discontinued at Week 96 MVC+ATV/r A a B C D E F b G H I FTC/TDF+ATV/r J K L 69 144 57 81 167 87 61 51 58 52 780 55 HIV-1 RNA, copies/mL Week 48 497 (W84) <50 (W96) <50 (W72) <50 (W84) <50 (W96) 274 (W96) <50 (W72) <50 (W84) <50 (W84) <50 (W84) <50 (W96) <50 (W84) Post Week 48

13. Change in median CD4+ cell count over time (LOCF) Median change from baseline in CD4 cell count (cells/μL) Study week 187 173 MVC + ATV/r (N=59) FTC/TDF + ATV/r (N=61) Intent-to-treat. LOCF, last observation carried forward

14. No genotypic or phenotypic resistance observed through Week 48 3 patients in the MVC arm and 3 patients in the FTC/TDF arm were identified for virologic analyses a a Patients who discontinued from the study early with sufficient VL (≥500 copies/mL). Assays (ESTA, Monogram GenoSeq and/or PhenoSenseGT) performed at screening/baseline and at the last on-treatment time point were available Change in tropism 0 Development of resistance mutations MVCATVTDFFTC 0000 Susceptibility to drug retained MVCFTC/TDF 33

15. Safety MVC + ATV/r n=60 FTC/TDF + ATV/r n=61 Any AE, n (%)58 (96.7)60 (98.7) Serious AE, n (%)10 (16.7)12 (19.7) Grade 3 or 4 AE, n (%)29 (48.3)18 (29.5) Discontinued due to AE, n (%)2 (3.3)0 Hyperbilirubinemia, n (%) AE related Grade 3 or 4 AE related Grade 3 or 4 laboratory* 27 (45.0) 22 (36.7) 39 (65.0) 21 (34.4) 12 (19.7) 32 (52.5) *DAIDS grading 7 patients in the MVC + ATV/r group and 3 patients in the FTC/TDF group switched off of ATV/r therapy per protocol due to either tolerability or unconjugated hyperbilirubinemia

16. Modern dual-therapy studies: 48-week results No. of patients with post-BL resistance mutations/no. of virologic failures a 22/46 39/56 16/78 0/0 3/3 HIV-1 RNA <50 copies/mL COOL 2 N=143 EFV +TDF EFV + TDF/3TC EFV + 2 NRTI EFV + LPV/r ACTG 5142 1 N=500 LPV/r + 2 NRTI 1. Riddler et al, N Engl J Med, 2008. 2. Girard et al, J Antimicrob Chemother, 2009. % of patients a from evaluable samples BL, baseline

17. Modern dual-therapy studies: 48-week results % of patients No. of patients with post-BL resistance mutations/no. of virologic failures a 22/46 39/56 16/78 0/0 3/3 HIV-1 RNA <50 copies/mL COOL 2 N=143 EFV +TDF EFV + TDF/3TC EFV + 2 NRTI EFV + LPV/r ACTG 5142 1 N=500 LPV/r + 2 NRTI LPV/r BID + FTC/TDF LPV/r BID + RAL BID SPARTAN 3 N=94 (2:1) ACTG 5262 5 N=112 PROGRESS 4 N=206 ATV BID + RAL BID DRV/r QD + RAL DRV/r QD + RAL BID ATV/r QD + FTC/TDF 0/8 4/11 1/3 1/4 5/28 a from evaluable samples BL, baseline 1. Riddler et al, N Engl J Med, 2008. 2. Girard et al, J Antimicrob Chemother, 2009. 3. Kozal THLBB204, IAS 2010. 4. Reynes MOAB0101, IAS, 2010. 5. Taiwo Abstract 551, CROI, 2011.

18. Modern dual-therapy studies: 48-week results No. of patients with post-BL resistance mutations/no. of virologic failures a 22/46 39/56 16/78 0/0 3/3 HIV-1 RNA <50 copies/mL COOL 2 N=143 EFV +TDF EFV + TDF/3TC EFV + 2 NRTI EFV + LPV/r ACTG 5142 1 N=500 LPV/r + 2 NRTI LPV/r BID + FTC/TDF LPV/r BID + RAL BID SPARTAN 3 N=94 (2:1) ACTG 5262 5 N=112 PROGRESS 4 N=206 ATV BID + RAL BID DRV/r QD + RAL DRV/r QD + RAL BID ATV/r QD + FTC/TDF 0/8 4/11 1/3 1/4 5/28 0/0 0/2 LPV/r BID + MVC QD LPV/r BID + FTC/TDF ATV/r QD + MVC QD ATV/r QD + FTC/TDF VEMAN 6 N=37 1078 N=121 1. Riddler et al, N Engl J Med, 2008. 2. Girard et al, J Antimicrob Chemother, 2009. 3. Kozal THLBB204, IAS 2010. 4. Reynes MOAB0101, IAS, 2010. 5. Taiwo Abstract 551, CROI, 2011. 6. Nozza CDB325, IAS, 2011 % of patients a from evaluable samples BL, baseline

19. Conclusions 48-week results of this pilot study of MVC + ATV/r support the antiviral activity of this once-daily, two-drug combination in treatment-naïve patients No resistance nor change in phenotypic tropism was observed No new unexpected safety events A Phase III study (A4001095; NCT01345630) will start in Q3/4 2011 –MVC + DRV/r QD vs FTC/TDF + DRV/r QD –Estimated enrollment of 804

20. Acknowledgments Thanks to the patients and investigators who participated in this study Editorial support was provided by Clemence Hindley of Complete Medical Communications and was funded by ViiV Healthcare

21. Backups

22. Creatinine clearance Study week Mean change from baseline in creatinine clearance (mL/min) MVC + ATV/r (N=60) FTC/TDF + ATV/r (N=61)

23. Pharmacokinetics Hours 04812162024 * 7.65 ng/mL (in vivo IC 50 ) 1 1 10 100 1000 10,000 MVC concentration (ng/mL) All 15 patients had plasma MVC concentrations above the in vivo IC 50 across the dosing Interval (150 mg QD + ATV/r) 2 There were 139 sparse PK samples with full dose and time data collected at the 2,12 and 24 week visits yielding concentrations from 13.7 to 933 ng/mL with samples taken from 0-32 hours after dose 3 * One patient accidentally dosed with MVC prior to the 24-hour sample draw 1. Rosario et al, J Acquir Immune Defic Syndr, 2006. 2. Vourvahis, Abstract 37 IWCPHIV, 2010. 3. Weatherley, Abstract P_05 IWCPHIV, 2011

24. Definition of Virologic Failure HIV-1 RNA <1.0 log10 decrease from Baseline at Week 4 or thereafter (confirmed by a second measurement taken no more than 14 days after the first measurement); or Failure to achieve HIV-1 RNA <400 copies/mL at Week 24, (confirmed by asecond measurement taken no more than 14 days after the first measurement); An increase in HIV-1 RNA to detectable levels (1,000 copies/mL on 2 consecutive measurements taken no more than 14 days apart) in subjects previously confirmed to have undetectable levels of <400 copies/mL on 2 consecutive visits.

25. Patients switching from ATV/r 10 patients switched from ATV/r (7 in the MVC arm and 3 in the FTC/TDF arm) due to either tolerability issues or unconjugated hyperbilirubinemia –8 switched to DRV/r –2 switched to LPV/r All 10 patients had reached HIV-1 RNA <50 copies/mL prior to switching

26. HIV-1 RNA <50 copies/mL at Week 24 and Week 48 according to baseline CD4 count 5/54/540/48n/N46/49

27. Median CD4+ cell count over time (LOCF) Median CD4 cell count (cells/mm 3 ) Study week Week 48 MVC + ATV/r = 580 FTC/TDF + ATV/r = 580 MVC + ATV/r (N=59) FTC/TDF + ATV/r (N=61) Intent-to-treat. LOCF, last observation carried forward Week 24 MVC + ATV/r = 537 FTC/TDF + ATV/r = 536

28. Responders at Week 24 but not Week 48 HIV-1 RNA, copies/mL Week 24Week 32Week 40Week 48 MVC+ATV/r ABCDABCD <50 <50 <50 56 <50 <50 <50 57 <50 <50 144 81 61 58 FTC/TDF+ATV/r EaFGHaEaFGHa <50 <50 N/A <50 <50 <50 N/A 780 b 55 N/A N/A, not available; W, week a Patient discontinued prior to Week 48 b Result of repeat test 13 days later was <50 copies/mL

29. Responders at Week 24 but not Week 48 HIV-1 RNA, copies/mL Week 24Week 32Week 40Week 48Post Week 48 MVC+ATV/r ABCDABCD <50 <50 <50 56 <50 <50 <50 57 <50 <50 144 81 61 58 <50 (W96) <50 (W84) <50 (W72) <50 (W84) FTC/TDF+ATV/r EaFGHaEaFGHa <50 <50 N/A <50 <50 <50 N/A 780 b 55 N/A N/A <50 (W96) <50 (W84) N/A N/A, not available; W, week a Patient discontinued prior to Week 48 b Result of repeat test 13 days later was <50 copies/mL 7/9 (MVC + ATV/r) and 3/3 (FTC/TDF + ATV/r) patients with HIV-1 RNA ≥50 copies/mL at Week 48 had HIV-1 RNA <50 copies/mL at their latest visit. HIV-1 RNA levels for the remaining 2 patients were 274 copies/mL (W96), and 497 copies/mL (W84)