P17.29 UGT1A1*6 polymorphisms are predictive of high plasma concentrations of dolutegravir in Japanese individuals. (13th September 2015)

• Record Type: Journal Article
• Authors: Yagura, H; Watanabe, D; Ashida, M; Kushida, H; Tomishima, K; Hirota, K; Ikuma, M; Yajima, K; Kasai, D; Nishida, Y; Uehira, T; Yoshino, M; Shirasaka, T
• Is Part Of: Sexually transmitted infections. Volume 91(2015)Supplement 2
• Page Start: A234
• Page End: A234
• Publication Date: 2015-09-13
• Subjects: Sexually transmitted diseases -- Periodicals; HIV infections -- Periodicals; 616.951005
• DOI: 10.1136/sextrans-2015-052270.607
• Languages: English
• ISSNs: 1368-4973

Abstract

Abstract : Background: Dolutegravir (DTG), an HIV integrase inhibitor, is metabolised mainly by glucuronidation via UDP-glucuronosyltransferase 1A1 (UGT1A1). Several UGT1A1 polymorphisms have been correlated with UGT1A1 expression level or enzymatic activity. We compared the effect of two polymorphic alleles in this gene, UGT1A1*6 and UGT1A1*28, on plasma DTG concentrations in Japanese HIV-1-infected patients. Methods: The plasma trough DTG concentration was measured in 69 HIV-1 patients taking DTG at Osaka National Hospital, and UGT1A1 genetic screening (*6 and *28) was performed. UGT1A1 was genotyped using the sequence method. Plasma was sampled immediately before taking DTG, and plasma DTG concentrations were determined using a liquid chromatography-mass spectrometry. Results: In the 69 patients who received DTG, the frequencies of UGT1A1*6 and UGT1A1*28 were 23% and 13%, respectively. The plasma trough concentrations of DTG in patients homozygous for UGT1A1*6 (n = 7, median: 1.4 µg/mL) were significantly higher those in the patients carrying the normal allele (n = 32, median: 0.89 µg/mL; p = 0.011). The plasma trough concentrations of DTG in patients homozygous for UGT1A1*28 (n = 3, median: 1.2 µg/mL), compound heterozygous for UGT1A1*6 and UGT1A1*28 (n = 2, 0.98 and 1.2 µg/mL, respectively), and heterozygous for UGT1A1*6 and UGT1A1*28 (n = 15 and 10, median: 1.1 and 1.0 µg/mL, respectively) were not significantly different from those in the patients homozygous for the normal allele. Conclusion: The plasma trough concentration of DTG was significantly higher in patients who were homozygous for UGT1A1*6 than in those with the normal allele. This finding suggests that the presence of UGT1A1*6 influences the plasma DTG concentration. Disclosure of interest statement: Authors do not have any commercial or other association that might pose a conflict of interest.