DART II Once Daily Regimen for Treatment-naïve HIV+ Patients with Stavudine XR + Lamivudine + Efavirenz 24 Week Interim Efficacy and Safety Results D aily A nti R etroviral T herapy II D. Jayaweera 1, S. Becker 2, F. Felizarta 3, M. Sands 4, L. Slater 5 S. Gothelf 6, J. Maa 6, C. Dezii 6, S. Hodder 6, J. Tudor 6 1 University of Miami, Miami, FL, USA. 2 Pacific Horizon Medical Group, San Francisco, CA, USA. 3 34th Street Community Health Center, Bakersfield, CA, USA. 4 University of Florida, Jacksonville, FL, USA. 5 University of Oklahoma, Oklahoma City, OK, USA. 6 Bristol-Myers Squibb, Plainsboro, NJ, USA.

DART II AI and -099 Study Outlines ARV-naive patients Randomized d4T XR 100mg QD d4T IR 40mg BID Patients <60 kg: d4T XR 75 mg QD; d4T IR 30 mg BID NFV substitution permitted if EFV-intolerant Adapted from: Brett-Smith H et al. 43rd ICAAC, September, Poster H-843 Study 096n=74n=76 Study 099n=392 (d4T IR placebo BID) 3TC 150mg BID EFV 600mg QD (d4T XR placebo QD) 3TC 150mg BID EFV 600mg QD

DART II Selected Adverse Events of Interest for Patients on Therapy for  2 Years Any Lipoatrophy (Any Grade) 64 (14%)36 (8%) Any Lipodystrophy (Any Grade) 73 (16%)52 (11%) Lactic Acidosis Syndrome Pancreatitis Peripheral Neurologic Symptoms (Grades 2-4) 1 (<1%) 4 (1%) 38 (8%) 1 (<1%) 17 (4%) Symptomatic Hyperlactatemia 5 (<1%)2 (<1%) d4T XR arm n=466 d4T IR arm n= 468 Study 096/099/110 * P-Value Adapted from: Brett-Smith H et al. 43rd ICAAC, September, Poster H-843 * Median follow up is 116 weeks XR and 114 weeks for IR

DART II d4T XR 100 mg Once Daily Comparable Drug Exposure to d4T IR 40 mg BID TIME [h] PLASMA CONCENTRATION [ng/mL] d4T IR d4T XR Peak (C max ) for d4T XR is ~50% of the IR formulation d4T XR formulation has 2-3 times higher trough plasma levels than d4T IR * Parallel groups for XR and IR formulations in HIV patients

DART II Prospective, once-daily, open-label, ARV-Naïve patients, VL > 1000 c/mL, CD4 > 100 Planned N= 70 Patients <60 kg: d4T XR 75 mg QD DART II: Study Design d4T XR 100 mg QD 3TC 300 mg QD EFV 600 mg QD + + Epivir ® (lamivudine, 3TC) is a registered trademark and manufactured by GlaxoSmithKline

DART II DART II: OBJECTIVES Efficacy of once daily d4T XR + 3TC + EFV as determined by proportion of patients with plasma HIV-RNA <400 copies/mL at 48-weeks Primary Objective: Secondary Objective: Proportion of patients with plasma HIV-RNA <400 and <50 copies/mL at Weeks 24, 48, 72, and 96 Patient adherence using pill counts and Antiviral Medication Adherence Form (AMAF) Safety and tolerability

DART II Baseline Characteristics d4T XR QD 3TC QD + EFV QD (N=64) Median Age, (years) Male White Black Other 83% 42% 45% 13% Median HIV RNA (log 10 copies/mL)4.7  100,000 copies/mL 30% Median CD4 Counts (cells/  L) 315 Demography Clinical 37

DART II Patient Disposition at Week 24 Evaluable Total Discontinuations, n (%) Reasons for Discontinuation Adverse Event Serious Adverse Event Death 10 (16%) 3 (5%) 0 0 Withdrew Consent4 (6%) 64 Lost to Follow-up2 (3%) Virologic Failure1 (2%) d4T XR QD 3TC QD + EFV QD

DART II Virologic Response HIV RNA <400 copies/mL : Baseline to Week Weeks Percent of Patients 94.3% 78.1% As Treated (n=54) ITT (NC=F) (n=64)

DART II Virologic Response HIV RNA <50 copies/mL: Baseline to Week Weeks Percent of Patients 94.3% 78.1% As Treated (n=54) ITT (NC=F) (n=64)

DART II Mean Change in HIV RNA Level: Baseline to Week 24 HIV RNA Change (log 10 copies/mL) Weeks

DART II CD4 Cell Mean Change: Baseline to Week 24 CD4 Mean Change (cells/mm 3 ) Weeks CD4 cell count Baseline: 354 Week 24:

DART II Grade Treatment Related Adverse Events (>2%) d4T XR + 3TC + EFV n=64 Vomiting2 (3.1%) Nausea Diarrhea Somnolence 4 (6.3%) 2 (3.1%) Grade 2-4 Hypoaesthesia3 (4.7%) Peripheral Neuropathy2 (3.1%)

DART II Treatment Related Adverse Events of Interest d4T XR + 3TC + EFV n=64 Pancreatitis0 Peripheral Neuropathy Lipodystrophy Symptomatic Hyperlactatemia Lactic Acidosis Syndrome 2 (3.1%) All Grades

DART II Grade 3-4 New Onset Laboratory Abnormalities d4T XR + 3TC + EFV n=64 Lipase Creatine Kinase ALT ANC 3 (4.7%) 2 (3.1%) 1 (1.6%) Grade 3-4 * No report of Grade 3-4 triglyceride levels

DART II Fasting Lipid Values Median Change from Baseline Baseline Total Cholesterol (mg/dL) 162 Median Change (%) (17%) LDL Cholesterol (mg/dL) (11%) Triglycerides (mg/dL) (-0.9%) HDL Cholesterol (mg/dL) ( 25%) P-value TC:HDL Ratio (- 8%) Median Values (N=32) Overall Results

DART II Summary of Adherence and Compliance at 24 Weeks d4T XR + 3TC +EFV Did not miss any dose during the past 4 days. 82.3% (51/62) Any time took fewer pills per dose 5.6% (3/54) Follow specific schedule 80.8% (42/52) d4T XR n=53  80% Compliance at Week 24 89% 3TC n=53 91% EFV n=53 89% Adherence (by AMAF * questionnaire) Compliance (by pill count)  90% Compliance at Week 24 70% 72% * Antiviral Medication Adherence Form

DART II Conclusions: 24 Weeks Demonstrated a significant reduction in viral load and excellent efficacy: 78.1% of patients achieved viral loads <400 copies/mL and <50 copies/mL (ITT: NC=F) 94.3% of patients achieved viral loads <400 copies/mL and <50 copies/mL (As Treated analysis) Is well tolerated Minimal discontinuations due to adverse events (n=3) Increase in HDL cholesterol, and decrease in TC:HDL ratio, with minimal effects on triglyceride levels In this treatment-naive population, d4T XR + 3TC + EFV administered once daily:

DART II TO ALL THE PATIENTS AND STUDY CENTER PARTICIPANTS Acknowledgments Stephen Becker, MD. San Francisco, CA Coordinator: Sunita Lundy Nicholaos Bellos, MD. Dallas, TX Coordinators: Christopher Hayes Dawn Chaney Paul Cook, MD. Greenville, NC Coordinator: Grace Wilkins, RN Franco Felizarta, MD. Bakersfield, CA Coordinator: Jennifer Kuhach Dushyantha Jayaweera, MD. Miami, FL Coordinator: Rose Lalanne, RN Gary Richmond, MD. Ft. Lauderdale, FL Coordinator: Vernon Appleby, RN Michael Sands, MD. Jacksonville, FL Coordinator: Debbie Aragon, RN Kunthavi Sathasivam, MD. Washington, DC Coordinator: Takada Harris Leonard Slater, MD. Oklahoma City, OK Coordinator: Brenda Verel, LPN