Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients

Pharmacogenomics J. 2013 Dec;13(6):484-9. doi: 10.1038/tpj.2012.46. Epub 2012 Oct 23.


We investigated the effects of pharmacogenetic variations and efavirenz pharmacokinetics on inter-individual differences in the extent of CYP3A induction by efavirenz using 4β-hydroxycholesterol/cholesterol (4β-OHC/Chol) as a marker for CYP3A induction. Plasma 4β-hydroxycholesterol and cholesterol concentrations were determined at baseline, and at the 4th, 16th and 48th week of efavirenz-based highly active antiretroviral therapy in antiretroviral therapy-naive HIV patients (n=77). Efavirenz plasma concentrations were quantified at weeks 4 and 16. CYP2B6, CYP3A5, ABCB1, UGT2B7 genotyping were done. Compared with baseline, the median plasma 4β-OHC/Chol ratio increased at the 4th (257%), 16th (291%) and 48th (165%) week (P<0.0001). CYP2B6*6 genotype significantly influenced 4β-OHC/Chol ratio at weeks 16 (P=0.02) and 48 (P=0.04) being highest in CYP2B6*6/*6>*1/*6>*1/*1. There were positive correlations between plasma efavirenz and 4β-OHC/Chol ratios (week 4: P=0.02, week 16: P=0.001). CYP3A enzyme induction by efavirenz is pronounced in CYP2B6 slow metabolizers who have high efavirenz plasma exposure.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Benzoxazines / therapeutic use*
  • Cyclopropanes
  • Cytochrome P-450 CYP3A / biosynthesis*
  • Cytochrome P-450 CYP3A / genetics
  • Enzyme Induction
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / enzymology
  • Humans
  • Male
  • Prospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*


  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Reverse Transcriptase Inhibitors
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • efavirenz