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Efavirenz plasma concentrations and cytochrome 2B6 polymorphisms.

Tristan Lindfelt1, John O'Brien, Jessica C Song

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Efavirenz concentrations varied by ethnicity and CYP2B6 genotype. Latino patients had higher midpoint efavirenz levels, while specific CYP2B6 variants influenced trough concentrations in HIV patients.

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Area of Science:

  • Pharmacogenomics
  • HIV/AIDS Therapeutics
  • Clinical Pharmacology

Background:

  • Interpatient variability in efavirenz (EFV) concentrations is linked to CYP2B6 genetic polymorphisms.
  • Limited pharmacogenomic data exists for efavirenz in Latino populations.

Purpose of the Study:

  • To compare trough and midpoint efavirenz plasma concentrations between HIV-positive Latino and white patients.
  • To investigate the association between efavirenz concentrations and CYP2B6 polymorphisms in these ethnic groups.

Main Methods:

  • Pilot study with 10 Latino and 10 white HIV-positive subjects.
  • Measurement of trough and midpoint efavirenz plasma concentrations.
  • Analysis of CYP2B6 genetic polymorphisms at codons 516 and 785 using Mann-Whitney and Kruskal-Wallis tests.

Main Results:

  • Midpoint efavirenz concentrations were significantly higher in Latino patients compared to white patients (p < 0.05).
  • Trough concentrations did not differ significantly by ethnicity.
  • Specific CYP2B6 variants (516TT, 516GT, 785GG, 785AG) were associated with significantly higher trough efavirenz concentrations (p < 0.05).

Conclusions:

  • Midpoint efavirenz concentrations are significantly higher in Latino individuals.
  • Trough efavirenz concentrations are influenced by specific CYP2B6 genetic variants (516 and 785).
  • Findings highlight ethnic and genetic factors affecting efavirenz pharmacokinetics in HIV treatment.