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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
Statement of
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; Benzoxazines; Aryl Hydrocarbon Hydroxylases; Oxidoreductases, N-Demethylating; P-Glycoproteins; P-Glycoprotein; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Treatment Outcome; Pharmacogenetics; Polymorphism, Single Nucleotide; African Continental Ancestry Group; European Continental Ancestry Group; Hispanic Americans; Female; Male; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP2B6
Rights: © 2010 by the Infectious Diseases Society of America
RMID: 0020105235
DOI: 10.1086/655470
Appears in Collections:Pharmacology publications

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