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

J Infect Dis. 2010 Sep 1;202(5):717-22. doi: 10.1086/655470.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • African Continental Ancestry Group
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Benzoxazines / pharmacokinetics*
  • Benzoxazines / therapeutic use
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A / genetics*
  • European Continental Ancestry Group
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / ethnology
  • HIV Infections / genetics
  • Hispanic Americans
  • Humans
  • Male
  • Oxidoreductases, N-Demethylating / genetics*
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Reverse Transcriptase Inhibitors / pharmacokinetics*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-HIV Agents
  • Benzoxazines
  • Reverse Transcriptase Inhibitors
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • efavirenz

Grant support