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.