Abstract

E-mail Abstract Author Add To Itinerary Session Search Abstracts Program

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

11:15   6. Study DPC 083-203, a Phase II Comparison of 100 and 200 mg Once-Daily DPC 083 and 2 NRTIs in Patients Failing a NNRTI-Containing Regimen N. Ruiz*1, R. Nusrat1, E. Lauenroth-Mai2, D. Berger3, C. Walworth4, L. T. Bacheler1, L. Ploughman1, P. Tsang1, D. Labriola1, R. Echols1, R. Levy1, and the DPC 083-203 Study Team 1Bristol-Myers Squibb Co., Wilmington, DE and Wallingford, CT; 2Berlin, Germany; 3Northstar Med. Ctr., Chicago, IL; 4Orange Coast Med. Group, Newport Beach, CA Background: Patients failing a NNRTI-containing regimen cannot be successfully treated with currently available NNRTIs. DPC 083 is an investigational NNRTI with potent activity against wild type HIV and greater potency against NNRTI-resistant mutations than efavirenz (EFV). Once-daily doses of 100 mg or 200 mg provide trough plasma concentrations likely to suppress replication of HIV-1 with the K103N mutation and frequently observed double mutants in NNRTI-containing regimen failures. This activity against mutant HIV-1 may result in virologic responses in NNRTI treatment-experienced patients. Methods: This is an ongoing study in patients failing a NNRTI-containing regimen with plasma HIV RNA > 1000 copies/Ml. Patients treated in the United States all received 100 mg once daily and patients in Europe were randomized to receive either 100 or 200 mg in a double-blind fashion. All patients received 2 NRTIs selected based on baseline genotype and treatment history. An analysis at week 8, blinded to dose, is presented. Results: 51 patients (mean age 40, 94% male) had (mean) baseline viral load (VL) log10 3.85 copies/mL and 473 CD4 cells/mm3; 61% had failed nevirapine and 39% had failed EFV. Baseline genotypic profiles, available on 48 patients, detected mutations in 94% of patients consistent with virologic failure on an NNRTI regimen including mutations at positions 101 (44%), 103 (52%), 181 (17%), and 190 (25%). The pooled (100 and 200 mg) on-treatment (OT) response rate at week 8 (< 400 copies/mL) was 57%. The mean change in VL from baseline was -1.28 log. The pooled OT response rates varied according to the number of new NRTIs used: no new NRTI 40% (4/10), 1 new NRTI 72% (13/18), and 2 new NRTIs 67% (10/15). The discontinuation rate due to adverse experiences was 16% (8/51). Conclusions: Responses at week 8 suggest that DPC 083 is active in patients who have failed marketed NNRTIs and harbor NNRTI-resistant mutations. Response rates appear to be higher when DPC 083 is used in combination with at least 1 new NRTI. DPC 083 was generally well tolerated.

©2002 9th Conference on Retroviruses and Opportunistic Infections