1. 1 RESIST Trials - Grade 3 or 4 AST, ALT or Total Bilirubin: Actions and Outcomes Action Taken: TPV/r N=748 CPI/r N=737 Total Number of Grade 3 or 4 ALT, AST, or Bilirubin 74 (9.9)26 (3.5) Continued treatment57 (7.6%)26 (3.5%) No interruption47 (6.3%)23 (3.1%) Interrupted10 (1.3%)3 (0.4%) Discontinued treatment17 (22.7%)0 (0%) With Grade 37 (0.9%) With Grade 410 (1.3%)

2. 2 Lipid Lowering Agent Use Among RESIST Participants Note: agents included are statins, fibrates, and omega-3 fatty acids n=108n=102n=130n=79n=238n=181 Use of Lipid Lowering Drugs in RESIST Percentage

3. 3 Effect of LLD on triglycerides: RESIST 390 (259, 581) 355 (230, 538) 445 (298, 634) 367 (286, 568) N6363118118 # deter3463

4. 4 Risk Confirmed (3 times) Triglycerides Above 500 mg/dl for RESIST Patients 17.26 8.20 0 2 4 6 8 10 12 14 16 18 04812162024283236404448 Exposure (weeks) TPV/rCPI/r Probability of event (%) Note: Included are RESIST participants who had baseline triglycerides <500 and developed at least 3 determinations above 500 mg/dL

5. 5 RTV-boosted drug interaction assessments

6. 6 Reduced GSS as Key Mutations Increase 0 10 20 30 40 50 60 70 01234 Number of key mutations % baseline background RTI susceptibility scores <2

7. 7 Hypertriglyceridemia: Relative Contribution of TPV and RTV Median baseline and maximal increase in serum triglycerides according to dose among Trial 1182.52 participants Dosen Median (Q25, Q75) baseline (mg/dL) Median (Q25, Q75) maximum increase (mg/dL) 500/10073263 (168, 430)161 (58, 403) 500/20072221 (172, 332)271 (99, 558) 750/20071223 (173, 416)196 (72, 421)

8. 8 Analysis of Treatment Response at Week 48 n = Number of responders N = Number of evaluable patients Treatment difference and confidence interval weighted for the size of enfuvirtide and PI strata RESIST-1RESIST-2 Treatment Group TPV/rCPI/rTPV/rCPI/r n(%)Nn Nn Nn N Key analysis FAS (week 24) (NCF, as randomised) 130(41.8)31174(23.9)309177(40.7)43576(17.8)428 FAS (week 48) (NCF, as randomised) 103(33.1)31149(15.9)309148(34.0)43564(15.0)428 Sensitivity analysis PPS (week 48) (NCF, as randomised) 66(35.7)18538(19.7)193102(37.4)27341(16.1)254

9. 9 K-M Probabilities for Grade 3 or 4 ALT and/or AST Through 120 Weeks in 8 HIV+ Integrated Trials* 29256210 187014451019417148133 # At Risk- Events- * Includes TPV/r patients from 1182.2, 1182.4, 1182.6, 1182.17, 1182.51, 1182.52, and CPI/r patients who switched to TPV/r 500/200 from RESIST trials 1182.12 and 1182.48

10. RESIST Studies Cox Regression Model for Risk of Grade 3 or 4 ALT/AST Baseline risk factors for Grade 3  4 ALT/AST are similar in TPV/r and CPI/r Independent variables: age, gender, race, ΔCD4, baseline triglycerides, NRTI, NNRTI, viral load, CDC HIV stage, duration of HIV infection Factor/Comparison Risk Ratio 95% CI Treatment Group: TPV/r vs CPI/r2.41.5 – 3.8 Baseline ALT,AST Total Bilirubin: (Grade > 1 vs Grade < 1)2.51.3 – 4.8 CD4+ Cell Count at Baseline: >200 vs ≤200 cells/mm 3 2.01.3 – 2.5 HBV or HCV Co-infection: Co-infected vs not co-infected2.31.4 – 3.7 10

11. 11 Predictors of TPV/r Antiviral Response Multiple Regression Model P ValueEstimate <0.010.17 TPV Score (per mutation) <0.01-0.24 Per Available Drug in OBR <0.01-0.91Enfuvirtide Use <0.01-1.25Tipranavir/r 24 Weeks Parameter

12. 12 Tipranavir trough concentrations with proton pump inhibitors

13. 13 Trial 1182.52 Impact of IQ on 14-Day Viral Load Response Change from baseline at 2 weeks (log 10 ) Inhibitory quotient Observed dataFold Change = 301 log 10 decline 30 -3 -2 0 1 0.1110100100010,000

14. 14 1182.52 Impact of IQ on 14-Day Viral Load Response 0.05 -0.13 -1.03 -1.16 -0.98 -1.25 -1.4 -1.2 -0.8 -0.6 -0.4 -0.2 0 ≤5≤5>5–30>30–50>50–100>100–150>150 Inhibitory quotient HIV RNA log 10 change from baseline 7 2714342558 0.2

15. 15 RESIST Trials 24 Week VL Change according to IQ in Patients not using Enfuvirtide

16. 16 RESIST Trials 24 Week VL Change according to IQ in Patients using Enfuvirtide

17. 17 Antiviral activity of tipranavir (ViroLogic) Non-clade B isolates Mean EC 50 (nM) 102 74 116 38 124 Ref. NL4-3 (B virus) EC 50 = 62 nM EC 50 values measured at ViroLogic Inc (South San Francisco) using the PhenoSense  assay No evidence that other HIV-1 clades and circulating recombinant forms have lower susceptibility to TPV than HIV-1 clade B Clade B biological cutoff value for TPV not yet determined (1.6X LPV or 99nM)* * Parkin et al, AAC, 2004, 48, 437-443 (three isolates each except two for clade H)

18. 18 VIRCO / ViroLogic in Tipranavir Phenotype

19. 19 Mutations Which Increase Susceptibility to TPV Amino acid Median FC IC 50 N Parameter Estimate P-value Wild typeMutated 18L1.000.505-0.550.035 30N1.200.5026-0.54<0.001 50V1.100.7019-0.310.021 54L1.100.7021-0.310.018 77I1.201.00102-0.180.011 88D1.100.6026-0.380.001