1. Mounir Ait-Khaled, 99767- 1 The Predictive Quality of Genotype and Phenotype Data on Virological Response to Salvage Therapy in HIV-1 Infected Patients (CNAA2007) Resistance Collaborative Group Reanalysis M Ait-Khaled, J Scott, L Dix, J Falloon, A Rakik, P Griffin, D Thomas and L Pedneault for the CNA2007 study team

2. Mounir Ait-Khaled, 99767- 2 Background Information Open-label, single arm trial of ABC (300mg BID) + APV (1200mg BID) + EFV (600mg QD) as salvage therapyOpen-label, single arm trial of ABC (300mg BID) + APV (1200mg BID) + EFV (600mg QD) as salvage therapy 101 subjects enrolled and 99 subjects exposed to study drugs101 subjects enrolled and 99 subjects exposed to study drugs Subjects had extensive prior antiretroviral experienceSubjects had extensive prior antiretroviral experience –44% were nNRTI experienced –60% had prior experience with 3-4 PIs –72% had prior experience with 4-5 NRTIs DemographyDemography –Median Age 42 years –84% males / 16% Females –82% White / 12% Black / 6% Other

3. Mounir Ait-Khaled, 99767- 3 Methods Plasma HIV-1 RNA: AmplicorPlasma HIV-1 RNA: Amplicor Genotyping; Plasma population sequencing (ABI)Genotyping; Plasma population sequencing (ABI) Phenotyping: Antivirogram (Recombinant Virus Assay)Phenotyping: Antivirogram (Recombinant Virus Assay) End Point: Week 24 HIV-1 RNA > 400 copies/mLEnd Point: Week 24 HIV-1 RNA > 400 copies/mL Statistical analysis according to DAPStatistical analysis according to DAP

4. Mounir Ait-Khaled, 99767- 4 Baseline Characteristics of Study Population Genotype Phenotype Population Population (N=94)(n=64) Median HIV-1 RNA5.0585.126 log 10 copies/mL(3.36-6.60)(3.99-6.33) (range) Median CD4 Count160124 cells/µL (range)(10-782)(10-607) Prior NNRTI Usage40%42%

5. Mounir Ait-Khaled, 99767- 5 Baseline HIV-1 Genotypes and Phenotypes of the Study Population 75% of isolates had  4 NRTI-associated mutations75% of isolates had  4 NRTI-associated mutations 45% had  1 NNRTI-associated mutation (21%  2)45% had  1 NNRTI-associated mutation (21%  2) 81% had  4 PI-associated mutation (50%  5)81% had  4 PI-associated mutation (50%  5) AbacavirAmprenavirEfavirenz < 4 Fold 45% 58% 67% < 10 Fold 94% 86% 73%

6. Mounir Ait-Khaled, 99767- 6 Genotypic Univariate Analysis: Odds Ratio of Virological Failure

7. Mounir Ait-Khaled, 99767- 7 Genotypic Multivariate Analysis: Odds Ratio of Virological Failure GSS with Additional Baseline Covariates

8. Mounir Ait-Khaled, 99767- 8 Genotypic Multivariate Analysis: Odds Ratio of Virological Failure Number of Mutations by Class with Additional Baseline Covariates

9. Mounir Ait-Khaled, 99767- 9 Phenotypic Univariate Analysis: Odds Ratio of Virological Failure

10. Mounir Ait-Khaled, 99767- 10 Phenotypic Multivariate Analysis: Odds Ratio of Virological Failure PSS with Additional Baseline Covariates

11. Mounir Ait-Khaled, 99767- 11 Phenotypic Multivariate Analysis: Odds Ratio of Virological Failure Class Phenotypic Sensitivities with Additional Baseline Covariates

12. Mounir Ait-Khaled, 99767- 12 Conclusions Genotypic Sensitivity Score was the only predictor of virological response in the model with Baseline RNA, New Drug Covariate and GSS (p=0.07).Genotypic Sensitivity Score was the only predictor of virological response in the model with Baseline RNA, New Drug Covariate and GSS (p=0.07). The number of NRTI and NNRTI mutations were also predictors of virological response after adjusting for baseline viral load and new drug covariate (p=0.03, 0.008, respectively).The number of NRTI and NNRTI mutations were also predictors of virological response after adjusting for baseline viral load and new drug covariate (p=0.03, 0.008, respectively). Continued

13. Mounir Ait-Khaled, 99767- 13 Conclusions (continued) In the univariate phenotypic analysis of this study the 4-fold but not the 10-fold cutoff was associated with virological failure.In the univariate phenotypic analysis of this study the 4-fold but not the 10-fold cutoff was associated with virological failure. In heavily pre-treated patients the Phenotypic Sensitivity Score using the 4-fold cutoff was the best predictor of response, independent of baseline viral load and new drug covariate.In heavily pre-treated patients the Phenotypic Sensitivity Score using the 4-fold cutoff was the best predictor of response, independent of baseline viral load and new drug covariate.

14. Mounir Ait-Khaled, 99767- 14 Investigators Joseph Eron, MD Judy Falloon, MD Judith Feinberg, MD Timothy Flanigan, MD Scott Hammer, MD Susan Jacobson, MD Peter Kraus, MD Robert Murphy, MD Ramon Torres, MD Glaxo Wellcome Mounir Ait-Khaled, PhD Seth Hetherington, MD Judith Millard, PhD Louise Pedneault, MD Mike Rogers, PhD William Spreen, Pharm D Deborah Thomas, PhD Margaret Tisdale, PhD Josie Wolfram, PhD Wendy Snowden, PhD Abdelrahim Rakik, MSc Philip Griffin, BSc NIH Henry Masur, MD DuPont Pharma Doug Manion, MD Betsy Dusak Statistics Janna Scott Lynn Dix Gillian Amphlett Richard Myers, MSc Acknowledgement

15. Mounir Ait-Khaled, 99767- 15 Backups

16. Mounir Ait-Khaled, 99767- 16 Genotypic Multivariate Analysis: Odds Ratio of Virological Failure Number of Mutations

17. Mounir Ait-Khaled, 99767- 17 Phenotypic Multivariate Analysis: Odds Ratio of Virological Failure Class Phenotypic Sensitivities