1. 1 Atazanavir (ATV) With Ritonavir (RTV) or Saquinavir (SQV) vs Lopinavir/Ritonavir (LPV/RTV) in Patients With Multiple Virologic Failures 24-Week Results From BMS AI424-045 R Badaro, E DeJesus, A Lazzarin, J Jemsek, B Clotet, A Rightmire, A Thiry, R Wilber

2. 2 Mean Plasma Concentration (SD) at Steady State (ng/mL) Supports selection of ATV 300/RTV QD dose for Phase III study in patients who failed multiple HAART regimens (BMS-045) Time (h) 04812162024 400 mg ATV 300 mg ATV/100 mg RTV 1 10 100 1000 10,000 75 th percentile 25 th percentile Median  22.6 ng/mL 4.8–3132.3 ng/mL Rationale for ATV 300 mg Boosted With RTV 100 mg in vitro Estimated Protein Adjusted EC 90 Range

3. 3 Study Objectives Primary –Compare magnitude of plasma HIV RNA reduction from baseline for ATV/RTV, ATV/SQV, and LPV/RTV in patients with multiple virologic failures Secondary –Virologic response rates: <400 and <50 c/mL through 24 weeks –CD4 cell count changes from baseline –Metabolic parameters: changes from Baseline Total cholesterol (TC) Fasting LDL cholesterol (LDL-C) HDL cholesterol (HDL-C) Fasting triglycerides (TG) –Safety and tolerability

4. 4 Study Design Wk 1-2 Wk 2-48 Patient Treatment History (N=358) Current Regimen PI or NNRTI Previous Regimens Failed  2 ARV History Failed  1 from each class Randomization 1:1:1 ATV 300mg QD RTV 100mg QD Maintain NRTIs TDF + 1 NRTI n=120 ATV 400mg QD SQV 1200mg QD Maintain NRTIs TDF + 1 NRTI n=115 LPV 400mg BID RTV 100mg BID Maintain NRTIs TDF + 1 NRTI n=123

5. 5 Patient Baseline Demography Age, median (yr) Female (%) Race (%) White Hispanic/Latino Black AIDS (%) HIV RNA, median (log 10 c/mL) CD4, median (cells/mm 3 ) 39 20 63 23 15 28 4.44 317 41 23 61 23 14 28 4.42 286 39 22 58 22 17 29 4.47 283 ATV 300/RTV n=120 ATV 400/SQV n=115 LPV/RTV n=123

6. 6 Patient Baseline Characteristics PI NRTI NNRTI 2.6 5.2 1.5 2.4 4.8 1.6 2.6 5.1 1.3 Prior ARV use, median ( Years ) ATV LPV 88 (74) 91 (76) 80 (73) 86 (78) 91 (77) Baseline susceptibility, n (%) PI NRTI 39 (33) 47 (39) 38 (33) 52 (45) 45 (37) 53 (43) Presence of  4 mutations at Baseline, n (%) ATV 300/RTV n=120 ATV 400/SQV n=115 LPV/RTV n=123

7. 7 Patient Disposition Treated, n Total discontinuations prior to Week 24, n (%) Adverse event Lost to follow up Non-compliance 119 7 (6) 4 (3) 0 0 110 14 (12) 5 (4) 2 (2) 118 6 (5) 2 (2) 0 ATV 300/RTV n=120 ATV 400/SQV n=115 LPV/RTV n=123 Protocol violation Patient withdrawal Treatment failure/lack of efficacy 0 2 (2) 1 (<1) 3 (3) 1 (<1) 2 (2) 0 0

8. 8 HIV RNA Mean Change From Baseline Through Week 24 ATV 300/RTV – LPV/RTV: 0.14 (-0.09, 0.37) ATV 400/SQV – LPV/RTV: 0.31 (-0.07, 0.55) -1.52 -1.86 -1.89 ATV 300/RTV (n=120) ATV 400/SQV (n=115) LPV/RTV (n=123) Time-Averaged Difference Estimate (97.5% Cl)

9. 9 Virologic Response Through Week 24 ATV 300/RTV – LPV/RTV: 2.4 (-9.8, 14.5) 39 42 62 64  400 ATV 300/RTV (n=120) LPV/RTV (n=123)  50 ITT: Time to Loss of Virologic Response Difference Estimate (95% Cl): <400 c/mL

10. 10 Virologic Response Through Week 24 ATV 300/RTV – LPV/RTV: 2.4 (-9.8, 14.5) 39 23 42 44 62 64  400 ATV 300/RTV (n=120) ATV 400/SQV (n=115) LPV/RTV (n=123)  50 ITT: Time to Loss of Virologic Response Difference Estimate (95% Cl): <400 c/mL

11. 11 62 42 * TLOVR: Time to Loss of Virologic Response 44 23 64 39 <400 copies/m <50 copies/mL Virologic Response at Week 24 % Responders (ITT: TLOVR*) ATV 300/RTV n=120 ATV 400/SQV n=115 LPV/RTV n=123

12. 12 Virologic Response at Week 24 ATV 300/RTV ATV 400/SQV ATV 300/RTV % of Responders * TLOVR: Time to Loss of Virologic Response % Responders (ITT: TLOVR*)

13. 13 CD4 Cell Mean Change From Baseline Through Week 24 90 83 59 ATV 300/RTV (n=120) ATV 400/SQV (n=115) LPV/RTV (n=123) ATV 300/RTV – LPV/RTV: -18.4 (-44.3, 7.5) ATV 400/SQV – LPV/RTV: -44.9 (-74.5, 15.3) Time-Averaged Difference Estimate (95% Cl)

14. 14 *Both ATV regimens vs LPV/RTV:P-value <0.0001 Lipids: Mean % Change From Baseline at Week 24 * * ATV 300/RTV LPV/RTV ATV 400/SQV Censoring: Patients on Lipid Lowering Therapy Excluded

15. 15 Use of Lipid Lowering Agents by Study Subjects 5 15 7 12 6767 Prior use On study ATV 300/RTV n=120 ATV 400/SQV n=115 LPV/RTV n=123 Use of Any Lipid Lowering Agent (%) P<0.005 P=NS

16. 16 Use of Lipid Lowering Agents by Study Subjects Use of Any Lipid Lowering Agent (%) P<0.005 P=NS % of Patients

17. 17 Grade 2-4 Related Adverse Events *No patients withdrew treatment due to jaundice Total, n (%) Diarrhea Jaundice Nausea 26 (22) 3 (3) 7 (6) 2 (2) 29 (26) 5 (5) 2 (2) 8 (7) 26 (22) 13 (11) 0 2 (2) ATV 300/RTV n=119 ATV 400/SQV n=110 LPV/RTV n=118 Vomiting Scleral icterus 0 4 (3) 4 (4) 0 1 (<1) 0 Withdrawal due to AE *4 (3)5 (4)2 (2) Grade 2-4 Related AEs (  5% of patients)

18. 18 Grade 3-4 Laboratory Abnormalities *No patients withdrew treatment due to bilirubin elevations Total bilirubin * ALT/SGPT AST/SGOT 54 (45) 4 (3) 20 (19) 4 (4) 2 (2) 1 (<1) 3 (3) 1 (<1) ATV 300/RTV n=119 ATV 400/SQV n=110 LPV/RTV n=118 Laboratory parameter n (%)

19. 19 Efficacy Summary ATV 300 mg boosted with RTV 100 mg once daily demonstrated efficacy similar to a standard of care (LPV/RTV) in the highly treatment-experienced patients through Week 24ATV 300 mg boosted with RTV 100 mg once daily demonstrated efficacy similar to a standard of care (LPV/RTV) in the highly treatment-experienced patients through Week 24 –ATV 400/SQV was less effective than LPV/RTV

20. 20 Metabolic Summary ATV boosted with RTV was associated with a more favorable lipid profile than LPV/RTVATV boosted with RTV was associated with a more favorable lipid profile than LPV/RTV –A 31% increase in TG was observed on LPV/RTV –Fewer patients treated with ATV/RTV required lipid- lowering agents than those on LPV/RTV –Total cholesterol decreased in the ATV/RTV arm compared with an increase on the LPV/RTV arm.

21. 21 Safety Summary ATV 300/RTV was safe and well toleratedATV 300/RTV was safe and well tolerated –Diarrhea was more common on LPV/RTV –Total bilirubin increases were not clinically significant, did not lead to treatment discontinuations, and was not associated with hepatotoxicity

22. 22 Conclusions ATV/RTV demonstrates efficacy similar to LPV/RTV in highly treatment- experienced patientsATV/RTV demonstrates efficacy similar to LPV/RTV in highly treatment- experienced patients ATV/RTV produces better lipid profiles compared to LPV/RTVATV/RTV produces better lipid profiles compared to LPV/RTV ATV is safe and well-toleratedATV is safe and well-tolerated

23. 23 Acknowledgments TO ALL THE PATIENTS AND STUDY CENTER PARTICIPANTS R Badaro, 1 E DeJesus, 2 A Lazzarin, 3 J Jemsek, 4 B Clotet, 5 A Rightmire, 6 A Thiry, 6 R Wilber 6 1 Hospital Universitario Prof. Edgard Santos, Salvador, Brazil; 2 IDC Research Initiative, Altamonte Springs, FL, USA; 3 Fondazione Centro S. Raffaele Del Monte Tabor, Milano, Italy; 4 Jemsek Clinic, Huntersville, NC, USA; 5 Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 6 Bristol-Myers Squibb, Wallingford, CT, USA