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Effect of CYP2B6, ABCB1, and CYP3A5 Polymorphisms on Efavirenz Pharmacokinetics and Treatment Response: An AIDS Clinical Trials Group Study

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
The Journal of Infectious Diseases
Vol. 202, No. 5 (1 September 2010), pp. 717-722
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/25706980
Page Count: 6
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Effect of CYP2B6, ABCB1, and CYP3A5 Polymorphisms on Efavirenz Pharmacokinetics and Treatment Response: An AIDS Clinical Trials Group Study
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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.

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