1. Superior Outcome for Tenofovir DF (TDF), Emtricitabine (FTC) and Efavirenz (EFV) Compared to Fixed Dose Zidovudine/Lamivudine (CBV) and EFV in Antiretroviral Naïve Patients JR Arribas 1, AL Pozniak 2, JE Gallant 3,E DeJesus 4, R Campo 5, B Gazzard 2, MJM Hitchock 6, B Lu 6, D McColl 6, J Enejosa 6 and A Cheng 6 for the Study 934 Team 1 Univ Hospital La Paz, Madrid, Spain; 2 Chelsea and Westminster Hosp., London, UK; 3 Johns Hopkins Univ School of Medicine, Baltimore, MD; 4 Orlando Immunology Center, Orlando, FL; 5 Univ Miami, Miami, FL; 6 Gilead Sciences, Foster City, CA 18 th International Conference on Antiviral Research 10 April 2005 Barcelona, Spain

2. Study 934 Study Design ART-naïve patients (n = 517) randomized 1:1 96 wks Any CD4 cell count HIV RNA > 10,000 c/mL TDFQD FTCQD EfavirenzQD AZT/3TCBID EfavirenzQD Adequate Renal and Hepatic Function at baseline FTC/TDF Fixed dose combination tablet was not used

3. Study 934 Statistical Analysis Non inferiority Trial Primary Endpoint < 400 c/mL at Week 48 -Time to Loss of Virologic Response (TLOVR) –FDA-required endpoint –Similar to ITT Missing = Failure, Switch = Failure –Requires confirmation for success –Used by FDA for presentation in U.S. Prescribing Information of newly approved antiretrovirals

4. a. Median values Study 934 Baseline Characteristics (ITT) FTC/TDF (n = 255) CBV (n = 254) Age a 3637 % Female14%13% % White56%61% % Black25%20% % Hispanic15%16% HIV RNA (log 10 copies/mL) a 5.0 % HIV RNA > 100,00052%50% CD4+ (cells/mm 3 ) a 233241 % < 20041% % < 5015%11%

5. Study 934 Study Population Never Dosed 6 Patients Treatment-experienced 2 Patients Randomized Population (n=517) ITT (n=509) Safety Population (n=511) Baseline NNRTI-R 22 Patients Modified ITT n=487

6. Study 934 Baseline NNRTI Resistance (ITT) 22 patients (11 FTC/TDF vs. 11 CBV) Investigators notified if affected FDA recommended excluding these patients for Week 48 primary endpoint analysis (n = 487) Primary Efficacy Endpoint (HIV RNA < 400 c/mL) at Week 48 analyzed for both populations, excluding NNRTI-R (n = 487) and ITT (n = 509)

7. Study 934 Summary Outcomes at Week 48 a. p value = 0.002 b. p value = 0.016

8. Study 934 Proportion with HIV-RNA <400 c/mL (TLOVR) ITT (n = 509) 0 20 40 60 80 100 BL81624324048 Weeks % Responder FTC/TDF 81%* CBV 70%* *95% CI: (+3.4%, +18.1%) p = 0.005 Exclude NNRTI-R (n=487): FTC/TDF 84%, CBV 73%, p=0.002 (+4.3%,18.6%)

9. Study 934 Proportion with HIV-RNA <50 c/mL (TLOVR) ITT (n = 509) 0 10 20 30 40 50 60 70 80 90 BL81624324048 Weeks % Responder FTC/TDF 77%* CBV 68%* *95% CI: (+0.9%, +16.2%) p = 0.034 Exclude NNRTI-R (n=487): FTC/TDF 80%, CBV 70%, p=0.021 (+1.6%,16.6%)

10. Study 934 CD4 Mean Absolute Change from Baseline As Treated FTC/TDF 190 CBV 158 FTC+TDF+EFV 238 234 223 218 209 198 CBV+EFV 222 216 199 188 175 164 0 75 125 175 225 BL81624324048 Weeks Mean Change (cells/mm 3 ) p = 0.002 at Week 48 p < 0.001 by AAUCMB

11. Study 934 Resistance Development in all Patients with >400 HIV RNA Copies/mL (mITT) 1.All patients (after wk 8) with confirmed >400 copies/mL of HIV RNA at Week 48 or early discontinuation analyzed. Patients w/ baseline NNRTI-resistance excluded (n = 22). Genotyping of 1 Combivir patient failed. 2.K103N developed in 21/25 patients. Other NNRTI mutations that developed included K101E, K103E, V108I, V179D, Y188H, G190A/S/E, P225H, M230L FTC/TDF, n=244 N, (% mITT) CBV, n=243 N (% mITT) Genotyping Population 1 12 (5%) 23 (9.5%) Any EFV-R 2 9 (4%) 16 (7%) Any M184V/I 2 (0.8%) 7 (3%) Any TAMs0 1 (0.4%) K65R00 Wild-type 3 (1%) 5 (2%)

12. a.Occurring in more than 1 patient in either arm; patients may have > 1 event b. p = 0.016 Study 934 Adverse Events Leading to Study Drug Discontinuation Through Week 48 Safety Population FTC/TDF (n = 257) CBV (n = 254) No. w/ any Adverse Event a 10 (4%)23 (9%) b Adverse Event Anemia/ ↓ Hgb014 (6%) Nausea1(<1%)4 (2%) Fatigue03 (1%) Vomiting02 (<1%) Dermatitis (NNRTI)2 (<1%)0 Neutropenia02 (<1%)

13. Study 934 Median (Range) Hemoglobin and Hematocrit Values Discontinuations due to Anemia on CBV arm (n=14) Hematocrit % 0 5 10 15 20 25 30 35 40 45 50 55 60 Baseline Nadir 40 47 31 22 33 11 0 2 4 6 8 10 12 14 16 18 20 Baseline Nadir Hemoglobin (g/dL) 13.8 16.0 10.8 6.9 3.7 9.3 0 2 4 6 8 10 12 14 16 18 20 Baseline Nadir Hemoglobin (g/dL) 13.8 16.0 10.8 6.9 3.7 9.3

14. Study 934 Serum Creatinine Maximum Confirmed Toxicity Grade (mg/dL) a FTC/TDF (n = 257) CBV (n = 254) 1 (>1.5 - 2.0)01 (<1%) 2 (2.1 - 3.0)01 (<1%) 3 (3.1 - 6.0)00 4 (>6.0)00 a. Confirmed toxicity grade = two consecutive visits

15. Superior overall response in the FTC/TDF arm compared to CBV arm No patient developed K65R M184V developed less frequently in the TDF/FTC arm than in the Combivir arm Significantly more CBV patients discontinued due to adverse events Similar renal safety profile No confirmed abnormalities in serum creatinine or phosphorus in FTC/TDF arm Study 934 Week 48 Summary