Effect of ABCB1 3435C>T transporter gene polymorphism on plasma efavirenz concentration in HIV-1 infected Thai adults

ABSTRACT

Objective: To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1. Methods: A single nucleotide polymorphism of ABCB1 3435C>T (rs1045642) in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment. Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration. The relationship between plasma efavirenz concentrations and ABCB1 3435C>T polymorphisms was analyzed. Results: Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age, gender, body weight, CD4 count and plasma HIV-1 RNA, blood biochemical parameters, antiretroviral duration or ABCB1 3435C>T polymorphisms, except for height (OR=0.902, 95% CI: 0.835-0.973) (PT was 0.446. The frequency of the heterozygous mutant ABCB1 3435C/ T was 53.02% (n=79), ABCB1 3435T/T homozygous mutant was 18.12% (n=27) and the wild type ABCB1 3435C/C genotype was 28.86% (n=43). The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L [IQR: (1.46-4.12) mg/L]. The plasma concentration of efavirenz was higher in cases with ABCB1 3435T/T homozygous mutant [2.73 mg/L, IQR: (2.02-4.19) mg/L] and ABCB1 3435C/T heterozygous mutant [2.29 mg/L, IQR: (1.41-4.28) mg/L] genotypes compared to the wild type ABCB1 3435C/C homozygous [2.1 mg/L, IQR: (1.37-3.53) mg/L]. However, there was no statistically significant difference in the efavirenz concentration between the different genotypes (P>0.05). Conclusions: There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB1 3435T/T and ABCB1 3435C/T genotypes. No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.