Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study.

Ribaudo HJ, Liu H, Schwab M, Schaeffeler E, Eichelbaum M, Motsinger-Reif AA, Ritchie MD, Zanger UM, Acosta EP, Morse GD, Gulick RM, Robbins GK, Clifford D, Haas DW
J Infect Dis. 2010 202 (5): 717-22

PMID: 20662624 · PMCID: PMC2919241 · DOI:10.1086/655470

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.

MeSH Terms (21)

African Continental Ancestry Group Alkynes Anti-HIV Agents Aryl Hydrocarbon Hydroxylases ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1 Benzoxazines Cyclopropanes Cytochrome P-450 CYP2B6 Cytochrome P-450 CYP3A European Continental Ancestry Group Female Hispanic Americans HIV Infections Humans Male Oxidoreductases, N-Demethylating Pharmacogenetics Polymorphism, Single Nucleotide Reverse Transcriptase Inhibitors Treatment Outcome

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