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https://hdl.handle.net/2440/63906
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Type: | Journal article |
Title: | Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study |
Author: | Ribaudo, H. Liu, H. Schwab, M. Schaeffeler, E. Eichelbaum, M. Motsinger-Reif, A. Ritchie, M. Zanger, U. Acosta, E. Morse, G. Gulick, R. Robbins, G. Clifford, D. Haas, D. |
Citation: | Journal of Infectious Diseases, 2010; 202(5):717-722 |
Publisher: | Univ Chicago Press |
Issue Date: | 2010 |
ISSN: | 0022-1899 1537-6613 |
Statement of Responsibility: | Heather J. Ribaudo, Huan Liu, Matthias Schwab, Elke Schaeffeler, Michel Eichelbaum, Alison A. Motsinger-Reif, Marylyn D. Ritchie, Ulrich M. Zanger, Edward P. Acosta, Gene D. Morse, Roy M. Gulick, Gregory K. Robbins, David Clifford, and David W. Haas |
Abstract: | In AIDS Clinical Trials Group protocols 384, A5095, and A5097s, we characterized relationships between 22 polymorphisms in CYP2B6, ABCB1, and CYP3A5; plasma efavirenz exposure; and/or treatment responses. A stepwise logistic regression procedure selected polymorphisms associated with reduced drug clearance adjusted for body mass index and the composite CYP2B6 516/983 genotype. Relationships between selected polymorphisms and treatment responses were characterized by competing risk methodology. Association analyses involved 821 individuals (317 for pharmacokinetics and 643 for treatment response). Models that included CYP2B6 516/983 genotype best predicted pharmacokinetics. Slow-metabolizer genotypes were associated with increased central nervous system events among white participants and decreased virologic failure among black participants. |
Keywords: | Humans HIV Infections Alkynes Cyclopropanes Benzoxazines Aryl Hydrocarbon Hydroxylases Oxidoreductases, N-Demethylating Reverse Transcriptase Inhibitors Anti-HIV Agents Treatment Outcome Pharmacogenetics Polymorphism, Single Nucleotide Female Male Cytochrome P-450 CYP3A Cytochrome P-450 CYP2B6 ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1 Hispanic or Latino White People Black People |
Rights: | © 2010 by the Infectious Diseases Society of America |
DOI: | 10.1086/655470 |
Grant ID: | RR000095 BRS-ACURE-06-00140-T001 AI51966 RR024996 AI062435 |
Published version: | http://dx.doi.org/10.1086/655470 |
Appears in Collections: | Aurora harvest Pharmacology publications |
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