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Short communication: lack of correlation between UGT1A1*6, *28 genotypes, and plasma raltegravir concentrations in Japanese HIV type 1-infected patients

Short communication: lack of correlation between UGT1A1*6, *28 genotypes, and plasma raltegravir concentrations in Japanese HIV type 1-infected patients

Aids Research and Human Retroviruses 28(8): 776-779

Raltegravir is metabolized by glucuronidation via UDP-glucuronosyltransferase 1A1 (UGT1A1). We analyzed the genotypes of UGT1A1 (*6, *27, and *28) and their contribution to plasma raltegravir concentrations in 56 Japanese HIV-1-infected patients in the National Hospital Organization Nagoya Medical Center of Japan. Among the 56 patients, the UGT1A1 genotype in two patients was *6 homozygote. Heterozygous variants were found in 13 patients for *6 and in 11 patients for *28, while all of the patients were found to carry wild-type sequences at the position corresponding to the *27 allele. Plasma raltegravir concentration of a male patient with *6 homozygote (0.53 μg/ml) was modestly higher than that of patients with wild type (0.12 μg/ml) or *6 heterozygote (0.16 μg/ml). Another female patient with the *6 homozygote had a low plasma raltegravir concentration (0.03 μg/ml). Patients heterozygous for the *6 or *28 allele did not display significantly different plasma raltegravir concentrations compared to patients homozygous for the respective wild-type allele. Thus, in the present study, we showed that heterozygous reduced-function *6 and *28 alleles appear to have no significant effect on plasma raltegravir concentrations in Japanese HIV-1-infected patients. However, variability in raltegravir concentration and small patient population precluded a correlation between UGT1A1*6 homozygosity and plasma raltegravir concentration. To clarify the contribution of UGT1A1*6 or *28 polymorphisms to plasma raltegravir concentrations, further investigations on larger subject populations are required.

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Accession: 055757778

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PMID: 21978357

DOI: 10.1089/aid.2011.0231

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