Kiyoto Tsuchiya

Bio: Kiyoto Tsuchiya is an academic researcher from Kumamoto University. The author has contributed to research in topics: Provirus & Virus. The author has an hindex of 16, co-authored 44 publications receiving 1068 citations. Previous affiliations of Kiyoto Tsuchiya include National Institutes of Health.

Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 *6 and *26

Abstract: Background Efavirenz (EFV) is metabolized primarily by cytochrome P450 2B6 (CYP2B6), and high plasma concentrations of the drug are associated with a G-->T polymorphism at position 516 (516G-->T) of CYP2B6 and frequent central nervous system (CNS)-related side effects. Here, we tested the feasibility of genotype-based dose reduction of EFV. Methods CYP2B6 genotypes were determined in 456 human immunodeficiency virus type 1 (HIV-1)-infected patients who were receiving EFV treatment or were scheduled to receive EFV-containing treatment. EFV dose was reduced in CYP2B6 516G-->T carriers who had high plasma EFV concentrations while receiving the standard dosage (600 mg). EFV-naive homozygous CYP2B6 516G-->T carriers were treated with low-dose EFV. In both groups, the dose was further reduced when plasma EFV concentration remained high. Results CYP2B6 516G-->T was identified in the *6 allele (found in 17.9% of our subjects) and a novel allele, *26 (found in 1.3% of our patients). All EFV-treated CYP2B6 *6/*6 and *6/*26 carriers had extremely high plasma EFV concentrations (>6000 ng/mL) while receiving the standard dosage. EFV dose was reduced to 400 mg for 11 patients and to 200 mg for 7 patients with persistently suppressed HIV-1 loads. EFV-containing treatment was initiated at 400 mg in 4 CYP2B6 *6/*6 carriers and one *6/*26 carrier. Two of them still had a high plasma EFV concentration while receiving that dose, and the dose was further reduced to 200 mg, with successful HIV-1 suppression. CNS-related symptoms improved with dose reduction in 10 of the 14 patients, although some had not been aware of the symptoms at initial dosage. Conclusions Genotype-based EFV dose reduction is feasible in CYP2B6 *6/*6 and *6/*26 carriers, which can reduce EFV-associated CNS symptoms.

Single Nucleotide Polymorphisms in ABCC2 Associate With Tenofovir-Induced Kidney Tubular Dysfunction in Japanese Patients With HIV-1 Infection: A Pharmacogenetic Study

Abstract: BACKGROUND Tenofovir is a widely used antiretroviral drug although it can cause kidney tubular dysfunction (KTD). The aim of this study was to determine the association between polymorphisms in genes encoding drug transporters and KTD in Japanese patients treated with tenofovir. METHODS The association between tenofovir-induced KTD and 14 single nucleotide polymorphisms (SNPs) in the ABCC2, ABCC4, ABCC10, SCL22A6, and ABCB1 genes was investigated in 190 Japanese patients. KTD was diagnosed by the presence of at least 3 abnormalities in the following parameters: fractional tubular resorption of phosphate, fractional excretion of uric acid, urinary β2-microglobulin, urinary α1-microglobulin, and urinary N-acetyl-β-D-glucosaminidase. Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays with standard protocols. Associations between genotypes and KTD were tested by univariate and multivariate logistic regression analyses. RESULTS KTD was diagnosed in 19 of the 190 (10%) patients. Univariate and multivariate analyses showed a significant association between KTD and genotype CC at position -24 CC (adjusted odds ratio [OR], 20.08; 95% confidence interval [CI], 1.711-235.7; P= .017) and genotype AA at position 1249 (adjusted OR, 16.21; 95% CI, 1.630-161.1; P= .017) of ABCC2. Multivariate analysis showed higher adjusted OR for patients with both homozygotes (adjusted OR, 38.44; 95% CI, 2.051-720.4; P= .015). ABCC2 haplotype -24T and 1249G was a protective haplotype for KTD (OR, 0.098; 95% CI, .002-.603; P= .003 CONCLUSIONS This is the first study of our knowledge to identify the association between SNPs in ABCC2 and tenofovir-induced KTD in an Asian population. Close monitoring of renal function is warranted in tenofovir-treated patients with these SNPs.

Integrative Genomics Viewer

Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Burden of HIV among female sex workers in low-income and middle-income countries: a systematic review and meta-analysis.

Abstract: Summary Background Female sex workers are a population who are at heightened risk of HIV infection secondary to biological, behavioural, and structural risk factors. However, three decades into the HIV pandemic, understanding of the burden of HIV among these women remains limited. We aimed to assess the burden of HIV in this population compared with that of other women of reproductive age. Methods We searched PubMed, Embase, Global Health, SCOPUS, PsycINFO, Sociological Abstracts, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and POPLine for studies of female sex workers in low-income and middle-income countries published between Jan 1, 2007, and June 25, 2011. Studies of any design that measured the prevalence or incidence of HIV among female sex workers, even if sex workers were not the main focus of the study, were included. Meta-analyses were done with the Mantel-Haenszel method with a random-effects model characterising an odds ratio for the prevalence of HIV among female sex workers compared with that for all women of reproductive age. Findings Of 434 selected articles and surveillance reports, 102 were included in the analyses, representing 99 878 female sex workers in 50 countries. The overall HIV prevalence was 11·8% (95% CI 11·6–12·0) with a pooled odds ratio for HIV infection of 13·5 (95% CI 10·0–18·1) with wide intraregional ranges in the pooled HIV prevalence and odds ratios for HIV infection. In 26 countries with medium and high background HIV prevalence, 30·7% (95% CI 30·2–31·3; 8627 of 28 075) of sex workers were HIV-positive and the odds ratio for infection was 11·6 (95% CI 9·1–14·8). Interpretation Although data characterising HIV risk among female sex workers is scarce, the burden of disease is disproportionately high. These data suggest an urgent need to scale up access to quality HIV prevention programmes. Considerations of the legal and policy environments in which sex workers operate and actions to address the important role of stigma, discrimination, and violence targeting female sex workers is needed. Funding The World Bank, UN Population Fund.