Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor hepatotoxicity

Clin Infect Dis. 2006 Sep 15;43(6):779-82. doi: 10.1086/507101. Epub 2006 Aug 15.

Abstract

This nested case-control study examined relationships between MDR1, CYP2B6, and CYP3A4 variants and hepatotoxicity during antiretroviral therapy with either efavirenz- or nevirapine-containing regimens. Decreased risk of hepatotoxicity was associated with MDR1 3435C-->T (odds ratio, 0.254; P=.021). An interaction between MDR1 and hepatitis B surface antigen status predicted risk with 82% accuracy (P<.001).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Benzoxazines
  • Case-Control Studies
  • Chemical and Drug Induced Liver Injury*
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • Genes, MDR*
  • Genetic Variation
  • Genotype
  • HIV Infections / drug therapy
  • HIV-1
  • Humans
  • Liver / drug effects
  • Liver Diseases / genetics
  • Liver Diseases / virology
  • Male
  • Nevirapine / adverse effects*
  • Nevirapine / metabolism
  • Nevirapine / therapeutic use
  • Oxazines / adverse effects*
  • Oxazines / metabolism
  • Oxazines / therapeutic use
  • Oxidoreductases, N-Demethylating / genetics
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Reverse Transcriptase Inhibitors / metabolism
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Oxazines
  • Reverse Transcriptase Inhibitors
  • Cytochrome P-450 Enzyme System
  • Nevirapine
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Oxidoreductases, N-Demethylating
  • efavirenz