110
Views
2
CrossRef citations to date
0
Altmetric
Original Research

A pharmacogenomic prospective randomized controlled trial of CYP2B6 polymorphisms and efavirenz dose adjustment among HIV-infected Thai patients: a pilot study

, , , &
Pages 155-162 | Published online: 03 Oct 2015
 

Abstract

Objective

We aimed at comparing clinical/immunological outcomes in human immunodeficiency virus (HIV)-infected patients who were treated with CYP2B6-guided and conventional efavirenz (EFV) therapy.

Methods

This study was a 24-week prospective randomized controlled trial. Eligible patients were HIV-infected adults yet to start antiretroviral therapy. Twenty-four HIV-infected patients were recruited and randomly assigned to genotype CYP2B6 polymorphism before ART initial dose. Patients with CYP2B6 *6/*6 received 400 mg EFV-based regimen and those with other genotypes received 600 mg EFV-based therapy.

Results

For CYP2B6 polymorphism, 12 patients were extensive metabolizers, ten patients were intermediate metabolizers, and only two patients were poor metabolizers (*6/*6). The overall mean EFV plasma concentrations were similar in both groups. The mean drug concentrations (standard deviation) were 1.675 (0.963), 1.445 (0.778), and 1.899 (0.808) µg/mL at week 4, 12, and 24, respectively. The CYP2B6 *6/*6 patient who received low dose of EFV had lower mean EFV level than those who received a normal dose, 1.916 versus 3.915 µg/mL (P<0.001), respectively. Seventy percent of the patients had neuropsychiatric adverse events, especially dizziness.

Discussion

There was a trend toward association of the CYP2B6 polymorphism and plasma EFV concentrations in this study. Reduced EFV dose should be considered in CYPB6 *6/*6 carrier to keep the drug concentration in therapeutic range.

Acknowledgments

This study was supported by research grant from the Faculty of Medicine Ramathibodi Hospital, Mahidol University and New Researchers Grant (MRG 5480136), The Mahidol University (MU)/the Thailand Research Fund and Office of the Higher Education Commission, and the Thailand Research Fund (TRF). The authors are also grateful to all patients who contributed to the study.

Disclosure

The authors report no conflicts of interest in this work.