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

TitleEffect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study.
Publication TypeJournal Article
Year of Publication2010
AuthorsRibaudo 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
JournalJ Infect Dis
Volume202
Issue5
Pagination717-22
Date Published2010 Sep 1
ISSN1537-6613
KeywordsAfrican Continental Ancestry Group, Anti-HIV Agents, Aryl Hydrocarbon Hydroxylases, Benzoxazines, Cytochrome P-450 CYP2B6, Cytochrome P-450 CYP3A, European Continental Ancestry Group, Female, Hispanic Americans, HIV Infections, Humans, Male, Oxidoreductases, N-Demethylating, P-Glycoprotein, P-Glycoproteins, Pharmacogenetics, Polymorphism, Single Nucleotide, Reverse Transcriptase Inhibitors, Treatment Outcome
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.

DOI10.1086/655470
Alternate JournalJ. Infect. Dis.
PubMed ID20662624
PubMed Central IDPMC2919241
Grant ListAI046376-05S4 / AI / NIAID NIH HHS / United States
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