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Low Raltegravir Concentration in Cerebrospinal Fluid in Patients With ABCG2 Genetic Variants

Tsuchiya, Kiyoto PhD*; Hayashida, Tsunefusa PhD*; Hamada, Akinobu PhD†,‡; Kato, Shingo PhD§; Oka, Shinichi MD, PhD*,‖; Gatanaga, Hiroyuki MD, PhD*,‖

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15th, 2014 - Volume 66 - Issue 5 - p 484–486
doi: 10.1097/QAI.0000000000000222
Brief Report: Basic and Translational Science

Abstract: Adenosine triphosphate–binding cassette transporter G2 (ABCG2) is expressed on the cerebrospinal fluid (CSF) side of choroid plexus epithelial cells, which form the blood–CSF barrier. Raltegravir was recently identified as a substrate of ABCG2. In the present study, we analyzed the relationship between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and raltegravir concentrations in 31 plasma and 14 CSF samples of HIV-infected patients treated with raltegravir-containing regimens. The mean CSF raltegravir concentration was significantly lower in CA (25.5 ng/mL) and AA (<10 ng/mL) genotypes at position 421 in ABCG2 gene compared with CC (103.6 ng/mL) genotype holders (P = 0.016).

*AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan;

Department of Clinical Pharmacology, Group for Translational Research Support Core, National Cancer Center Research Institute, Tokyo, Japan;

Department of Medical Oncology and Translational Research, Kumamoto University, Kumamoto, Japan;

§Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; and

Center for AIDS Research, Kumamoto University, Kumamoto, Japan.

Correspondence to: Hiroyuki Gatanaga, MD, PhD, AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (e-mail:

Supported by The Grant for National Center for Global Health and Medicine (H22-110) and a Grant-in-Aid for AIDS Research from the Japanese Ministry of Health, Labour and Welfare (H23-AIDS-001).

S.O. has received honoraria and research grants from MSD, Janssen Pharmaceutical, Abbott, Roche Diagnostics, and Pfizer and also honoraria from ViiV Healthcare, Torii Pharmaceutical, Bristol-Myers, Astellas Pharmaceutical, GlaxoSmithKline, Taisho Toyama Pharmaceutical, Dainippon Sumitomo Pharma, and Daiichisankyo. H.G. has received honoraria from MSD, Janssen Pharmaceutical, Abbott, ViiV Healthcare, and Torii Pharmaceutical. The remaining authors have no conflicts of interest to disclose.

Received January 16, 2014

Accepted April 23, 2014

© 2014 by Lippincott Williams & Wilkins