Influence of Polymorphism on Plasma Efavirenz Concentration in Thai HIV-1 Patients.

PURPOSE

Plasma efavirenz (EFV) concentrations within therapeutic levels are essential to successfully treat patients suffering from human immunodeficiency virus (HIV) type 1. In addition to the drug-metabolizing enzyme CYP2B6, other phase II drug-metabolizing enzymes and transporters may have an important role in the pharmacokinetics of EFV. Thus, the influence of phase II drug-metabolizing enzymes and drug transporters on plasma EFV levels was investigated in Thai HIV patients receiving EFV.

PATIENTS AND METHODS

Genotyping was performed by TaqMan real-time PCR in 149 HIV-infected Thai adults, and plasma efavirenz concentration was measured by a validated high-performance liquid chromatography in 12 hours after dosing steady-state plasma samples at week 12 and 24.

RESULTS

Patients with three or more copies of had significantly lower median plasma EFV concentrations than those carrying two copies at week 12 (=0.046) and (c.638G>A) carriers had significantly lower median plasma EFV concentrations compared to those not carrying the variant at week 24 (=0.048). However, no significant association was found after adjusting for genotype.

CONCLUSION

Genetic variation in a combination of and copy number may contribute to variability in EFV metabolism and thereby may impact drug response. The influence of a combination between the and genotype on EFV pharmacokinetics should be further investigated in a larger study population.