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Session 62 Poster Session Pharmacokinetics of Antiretroviral Drugs Session Time: 4:30-6:30 pm Room 4E-F

428-W. Racial Differences in Clinical Efficacy of Efavirenz-Based Antiretroviral Therapy S. Wegner*1, M. Vahey1, M. Dolan1, M. Wallace1, N. Aronson1, A. Barile1, W. Emmons1, S. Frazier1, K. Stephan1, M. Nau2, S. Piscitelli3, R. Harrigan4, and B. Larder4 1U.S. Military HIV Res. Prog., Rockville, MD; 2Henry M. Jackson Fndn., Rockville, MD; 3Vircolab, Gaithersburg, MD; and 4Virco-UK, Cambridge, UK Background: Different cytochrome P450 (CYP) 2D6 genotypes have been shown to predict marked difference in efavirenz (EFV) trough levels. CYP genotypes have different frequencies in different ethnic and racial groups. We sought to assess the relative clinical response duration in African American (AA) and Caucasian © HIV-1-infected subjects treated with EFV-based therapy, and to determine if differences could be explained by CYP genotype. Methods: 450 HIV-1-infected U.S. Department of Defense beneficiaries on 3 or more antiretroviral drugs including at least one NNRTI or PI were enrolled in a long-term study to assess the efficacy of resistance testing. Virologic failure was defined as either a rise in plasma viral load (VL) to > 3 logs in a subject with previously undetectable viral load, or a failure to suppress VL to < 3 logs by 16 weeks. 99 subjects (56 AA and 43 C) on efavirenz at enrollment were analyzed. Primary endpoint was time to virologic failure. 102 subjects who were on indinavir and 172 subjects on nelfinavir at time of enrollment were analyzed for comparison. Results: There were no differences in age, CD4 count, number of previous antiretroviral drugs, or number of previous NNRTI between racial groups at baseline. There were no differences in time to virologic failure between racial groups for subjects on nelfinavir (NLV) or indinavir (IDV) at enrollment. For AA subjects on efavirenz, median time to failure was reached at 422 days. For C subjects, median was not reached at 1400 days (Cox proportional hazard model risk ratio=2.42 (95% CI 1.35-4.57) p=.0027). No differences were observed between groups in mean fold resistance to efavirenz at failure. There were differences in CYP 2D6 genotypes between AA and C subjects, but these did not correlate with outcome. Conclusion: In our cohort of HIV-1-infected military health care beneficiaries with uniform access to health care, we have observed significant racial differences in time to virologic failure that appear to be specific for efavirenz-based therapy. These differences could not be explained by CYP 2D6 genotype. Absence of time-to-failure differences in groups treated with IDV and NLV suggest that there are not race-based differences in adherence in this cohort. Further pharmacokinetic analysis is planned.

©2002 9th Conference on Retroviruses and Opportunistic Infections