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Updated: Feb 23, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
High plasma concentrations of dolutegravir in patients with ABCG2 genetic variants
Kiyoto Tsuchiya1, Tsunefusa Hayashida, Akinobu Hamada
1aAIDS Clinical Center bDepartment of Pharmacy, National Center for Global Health and Medicine cDepartment of Clinical Pharmacology, Group for Translational Research Support Core, National Cancer Center Research Institute, Tokyo dDepartment of Medical Oncology and Translational Research eCenter for AIDS Research, Kumamoto University, Kumamoto, Japan.
Abstract:
The ATP-binding cassette transporters B1 (ABCB1) and G2 (ABCG2) are both expressed in the intestine and known as efflux transporters of drugs. Dolutegravir was identified recently as a substrate of both ABCB1 and ABCG2. This study aimed to determine the relations between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and plasma dolutegravir concentrations. Plasma samples were obtained from 42 HIV-1-infected patients treated with dolutegravir-containing regimens 0.5-4 h after dolutegravir dosing. Plasma dolutegravir concentrations were measured by liquid chromatography-mass spectrometry. Genomic DNA was isolated from peripheral blood mononuclear cells. Genotyping of allelic variants of ABCB1 1236 C>T (rs1128503), 2677 G>T/A (rs2032582), 3435 C>T (rs1045642), 4036 A>G (rs3842), and ABCG2 421 C>A (rs2231142) was performed using the TaqMan drug metabolism assays. None of the genotypes in ABCB1 1236 C>T, 2677 G>T/A, 3435 C>T, and 4036 A>G correlated with plasma dolutegravir concentration. In contrast, the mean peak plasma concentration of dolutegravir was significantly higher in the genotypes of ABCG2 421 AA (5002 ng/ml, n=3) compared with the genotypes of ABCG2 421 CC (2569 ng/ml, n=22) and ABCG2 421 CA (2479 ng/ml, n=17) (P=0.0005). The speculated peak level of plasma dolutegravir concentration was significantly higher in ABCG2 genetic variant holders, probably, at least in part, because of low expression levels of efflux transporters in the intestines associated with these genetic variants.
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