A pharmacogenomic prospective randomized controlled trial of CYP2B6 polymorphisms and efavirenz dose adjustment among HIV-infected Thai patients: a pilot study
Authors Damronglerd P, Sukasem C, Thipmontree W, Puangpetch A, Kiertiburanakul S
Received 11 April 2015
Accepted for publication 11 August 2015
Published 3 October 2015 Volume 2015:8 Pages 155—162
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Martin Bluth
Pansachee Damronglerd,1 Chonlaphat Sukasem,2,4 Wilawan Thipmontree,3 Apichaya Puangpetch,2,4 Sasisopin Kiertiburanakul1
1Deparment of Medicine, 2Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 3Department of Medicine, Faculty of Medicine, Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, 4Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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.
Keywords: CYP2B6 polymorphism, efavirenz, prospective study, Thai, HIV-infected patient, pharmacogenetics
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