Dose reduction of efavirenz: an observational study describing cost-effectiveness, pharmacokinetics and pharmacogenetics

Pharmacogenomics. 2014 May;15(7):997-1006. doi: 10.2217/pgs.14.48.

Abstract

Aim: Antiretroviral treatment implies a high cost to the healthcare system. The aim of this study was to evaluate the clinical and economic impact of efavirenz (EFV) dose adjustment by monitoring plasma concentrations and pharmacogenetic analysis of the 516G>T CYP2B6 polymorphism.

Materials & methods: One hundred and ninety HIV patients treated with EFV were studied. Plasma EFV concentrations were measured by HPLC with ultraviolet detection, and pharmacogenetic analysis was performed by Real Time (RT)-PCR.

Results: One hundred and ninety patients initially treated with a standard dose of EFV (600 mg/day) were studied. In 31 (16.3%) patients, EFV dose was reduced. A total of 87.1% of patients were heterozygous/homozygous carriers (GT/TT). CD4(+) count increased while the minimum steady-state plasma concentration and adverse effects decreased significantly after dose adjustment. Considering only the dose reduction, the adjustments accounted for a saving of 43,539 €/year.

Conclusion: The individualization of EFV dosage guided by genotyping 516G>T CYP2B6 and therapeutic drug monitoring could increase the efficiency of EFV use in antiretroviral treatment.

Keywords: CYP2B6; HIV; antiretroviral treatment; efavirenz; efficiency; pharmacogenetics; pharmacokinetics; therapeutic drug monitoring.

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics
  • Benzoxazines / administration & dosage*
  • Benzoxazines / pharmacokinetics
  • Cost-Benefit Analysis
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6 / genetics*
  • Drug Monitoring
  • Female
  • Genotype
  • HIV / drug effects
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / pathology
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • efavirenz