Association between polymorphisms of tenofovir transporters and tenofovir plasma levels in Thai HIV-infected patients

Abstract

Several factors including, body weight, kidney function and transporter polymorphisms are postulated that they can influence tenofovir levels. A present, there are no studies investigating the relationship between tenofovir transporter polymorphisms and these factors on drug plasma levels. This study aimed to investigate the influence of the ABCC2, ABCC4 polymorphisms and other factors, including body weight, glomerular filtration rate (GFR) and kidney tubular dysfunction (KTD) on tenofovir plasma levels. This is a cross sectional study performed in 106 patients who had stable tenofovir dosage regimen for at least 2 weeks. Tenofovir plasma levels were determined using HPLC method. Genotyping of ABCC2 and ABCC4 was carried out by Taqman allelic discrimination assays. Independent t-test was used to compare tenofovir plasma levels among groups of different polymorphisms. Multiple regression analysis was performed to investigate an association between factors and tenofovir plasma levels. The results found that tenofovir plasma levels of patients with wild type of ABCC4 3463A>G and 4131T>G were significantly different from patients with at least 1 variant allele. The stepwise regression model showed that weight and GFR influence tenofovir plasma levels. However, after adjusting for weight and GFR, the influence of ABCC4 polymorphisms was not found.