Effect ofCYP2B6,ABCB1, andCYP3A5Polymorphisms on Efavirenz Pharmacokinetics and Treatment Response: An AIDS Clinical Trials Group Study | Zendy

Heather J. Ribaudo | Zendy; Huan Liu | Zendy; Matthias Schwab | Zendy; Elke Schaeffeler | Zendy; Michel Eichelbaum | Zendy; Alison A. MotsingerReif | Zendy; Marylyn D. Ritchie | Zendy; Ulrich M. Zanger | Zendy; Edward P. Acosta | Zendy; Gene D. Morse | Zendy; Roy M. Gulick | Zendy; Gregory K. Robbins | Zendy; David B. Clifford | Zendy; David W. Haas | Zendy

Open Access

Effect ofCYP2B6,ABCB1, andCYP3A5Polymorphisms on Efavirenz Pharmacokinetics and Treatment Response: An AIDS Clinical Trials Group Study

Author(s) -

Heather J. Ribaudo,

Huan Liu,

Matthias Schwab,

Elke Schaeffeler,

Michel Eichelbaum,

Alison A. MotsingerReif,

Marylyn D. Ritchie,

Ulrich M. Zanger,

Edward P. Acosta,

Gene D. Morse,

Roy M. Gulick,

Gregory K. Robbins,

David B. Clifford,

David W. Haas

Publication year - 2010

Publication title -

the journal of infectious diseases

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.69

H-Index - 252

eISSN - 1537-6613

pISSN - 0022-1899

DOI - 10.1086/655470

Subject(s) - efavirenz , pharmacokinetics , cyp2b6 , logistic regression , medicine , cyp3a5 , genotype , clinical trial , pharmacology , pharmacogenetics , oncology , biology , immunology , cyp3a4 , genetics , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy , cytochrome p450 , metabolism , gene

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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