CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans

Eur J Clin Pharmacol. 2012 Mar;68(3):267-71. doi: 10.1007/s00228-011-1118-0. Epub 2011 Sep 8.


Objective: Efavirenz, an antiretroviral medicine, is extensively metabolized by cytochrome P450 2B6 (CYP2B6), UDP-glucuronosyltransferase 2B7 (UGT2B7), and CYP2A6. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in these genes with plasma efavirenz levels in Zimbabwean human immunodeficiency virus (HIV)-positive patients treated with efavirenz.

Methods: The exon regions of the CYP2B6, CYP2A6, and UGT2B7 genes were re-sequenced in 49 HIV-infected Zimbabwean patients treated with a combination therapy including efavirenz. Associations of SNPs in these three genes with efavirenz plasma concentrations 11-16 h after the administration of treatment were evaluated.

Results: Eight patients carrying CYP2B6*6/*18 showed the highest plasma efavirenz levels, with a fourfold higher concentration than patients who carried CYP2B6*1/*1. Patients with CYP2B6*6/*6 also showed higher efavirenz plasma concentrations than those with CYP2B6*1/*1. Among the 17 and 12 SNPs identified in CYP2A6 and UGT2B7, respectively, no SNP showed a significant association with the plasma efavirenz concentration.

Conclusion: Although based on only a limited number of subjects, our results suggest that the CYP2B6*6 and CYP2B6*18 alleles should affect hepatic metabolic activity and elevate the systemic circulation level of efavirenz, which may lead to toxicity in Zimbabwean HIV patients.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Anti-HIV Agents / blood*
  • Anti-HIV Agents / pharmacokinetics
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Benzoxazines / blood*
  • Benzoxazines / pharmacokinetics
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • Female
  • Genotype
  • HIV Infections / blood
  • HIV Infections / genetics*
  • Humans
  • Male
  • Oxidoreductases, N-Demethylating / genetics*
  • Polymorphism, Single Nucleotide
  • Reverse Transcriptase Inhibitors / blood*
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Zimbabwe


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Reverse Transcriptase Inhibitors
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • efavirenz