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Session 4 Oral Abstract Session Antiretroviral Chemotherapy: New Agents Session Time: Monday, 10 am - 12:30 pm Room 6A-B

11:30   7. Study DPC 083-201: A Phase II Double-Blind (DB) Comparison of 3 Once Daily Doses of the NNRTI DPC 083 vs 600 mg Efavirenz (EFV) in Combination with 2 NRTIs in HIV Anti-Retroviral (ARV) Treatment-Naïve Patients N. Ruiz*1, R. Nusrat1, A. Lazzarin2, K. Arasteh3, F-D. Goebel4, S. Audagnotto5, A. Rachlis6, J. R. Arribas7, L. Ploughman1, W. Fiske1, D. Labriola1, R. Levy1, and R. Echols1 for the DPC 083-201 Study Team 1Bristol-Myers Squibb, Wilmington, DE and Wallingford, CT; 2HS Raffaele, Milan, Italy; 3Vivantes Auguste-Viktoria-Hosp, Berlin, Germany; 4Poliklinik-Medizinische, Munich, Germany; 5 Hosp. Amedeo di Savoia, Torino, Italy; 6Sunnybrook Health Sci. Ctr., ON,Canada, 7Hosp. La Paz, Madrid, Spain Background: DPC 083 (083) is an investigational NNRTI with potent activity against wild type HIV and greater potency against NNRTI-resistant mutants than EFV. The objective of this study was to compare the tolerability of 3 doses of 083 to the standard dose of EFV in ARV-naïve patients. Pharmacokinetic and efficacy data were also analyzed. Methods: Study DPC 083-201 is an ongoing, multicenter, randomized, DB study comparing 50, 100, and 200 mg of 083 once-daily with EFV 600 mg once-daily each in combination with Combivir in HIV ARV-naïve patients (plasma HIV RNA > 1000 copies/mL and CD4 cell count > 200/mm3). A planned analysis of 24-week data is presented. Results: Enrolled patients (total 134, 85% male, 83% Caucasian, median age 35) had (median) baseline viral load 33,113 copies/mL and CD4 count 367 cells/mm3. The intent-to-treat (NC=F, < 50 copies/mL) response rates were: 79% (50 mg), 67% (100 mg), 72% (200 mg), and 78% (EFV). There were no statistically significant differences between the treatment groups (p > 0.05). Premature discontinuation rates were 14% (50 mg), 17% (100 mg), 24% (200 mg), and 22% (EFV) (p > 0.05chi2). Dizziness was less frequent with 083 (11-18%) than with EFV (32%). The frequency of rash was 15% (50 mg), 33% (100 mg), 53% (200 mg), 38% (EFV). All doses of DPC 083 provided median steady-state free plasma trough levels above the IC90 for K103N and many double mutants. The 100 mg and 200 mg doses provided median trough concentrations exceeding the IC90 for the K103N mutation after the first dose. Conclusions: DPC 083 was highly effective and well tolerated in ARV-naïve patients. Compared with EFV, occurrence of dizziness was lower and of rash, dose-related. DPC 083 provides free trough plasma levels that exceed the IC90 for virus containing key NNRTI-resistant mutations.

©2002 9th Conference on Retroviruses and Opportunistic Infections