https://orcid.org/0000-0003-3917-6567
Abstract
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 SULT1A1 had significantly lower median plasma EFV concentrations than those carrying two copies at week 12 (p=0.046) and SULT1A1*2 (c.638G>A) carriers had significantly lower median plasma EFV concentrations compared to those not carrying the variant at week 24 (p=0.048). However, no significant association was found after adjusting for CYP2B6 genotype.
Conclusion
Genetic variation in a combination of SULT1A1*2 and SULT1A1 copy number may contribute to variability in EFV metabolism and thereby may impact drug response. The influence of a combination between the SULT1A1 and CYP2B6 genotype on EFV pharmacokinetics should be further investigated in a larger study population.
Acknowledgments
This research is supported by the Faculty of Medicine, Ramathibodi Hospital, Mahidol University; The International Research Network-The Thailand Research Fund (IRN60W003), Thailand; Rachadapisek Sompote Fund for Postdoctoral Fellowship, Chulalongkorn University. The authors also thank the Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, and School of Medicine, University of Missouri–Kansas City, for providing access to quantitative multiplex PCR amplification.
Disclosure
The authors reported no conflicts of interest in this work.