Dataset Information

A Single-Nucleotide Polymorphism in ABCC4 Is Associated with Tenofovir-Related Beta2-Microglobulinuria in Thai Patients with HIV-1 Infection.

ABSTRACT: In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected individuals since 2001. Due to relatively frequent adverse effects, d4T gradually has been replaced with tenofovir disoproxil fumarate (TDF). Although the frequency of adverse drug effects with TDF is lower than that with d4T, TDF is known to induce kidney dysfunction, especially in the proximal tubules. It has been reported that renal tubular transporters, including members of the multi-drug resistant (MDR) protein family, are implicated in tenofovir extrusion and may, therefore, confer susceptibility to TDF-induced kidney tubular dysfunction (KTD). We have explored the association between KTD and polymorphisms in genes that encode adenosine triphosphate-binding cassette (ABC)-type MDRs.HIV-infected patients receiving TDF-containing antiretroviral regimens for at least one year were enrolled in the study. The levels of beta2-microglobulin in urine and creatinine (Cr) were measured. Three single-nucleotide polymorphisms, ABCC2 C-24T (rs717620), ABCC2 G1429A (rs2273697), and ABCC4 T4976C (rs1059751), were analyzed using TaqMan SNP genotyping assays.A total of 273 HIV-infected patients were recruited. The median number of years of TDF treatment was 5.04 with interquartile range (IQR) of 3.9-6.7. Despite the length of treatment with TDF, 98.5% patients maintained an estimated glomerular filtration rate (eGFR) of >60 mL/min as calculated by the CKD-EPI formula. Fifty-four patients (19.8%) showed beta2-microglobulinuria (median 2636 ?g/g Cr with IQR of 1519-13197 ?g/g Cr). The allele frequency of ABCC4 T4976C among those 54 patients was 0.602, compared to 0.475 among the 219 remaining patients (p = 0.018).Approximately 20% of HIV-infected patients receiving TDF showed beta2-microglobulinuria. The C allele at position 4976 of the ABCC4 gene was associated with beta2-microglobulinuria in this population. This polymorphism may help to identify patients at greater risk for developing TDF-associated KTD.

SUBMITTER: Likanonsakul S

PROVIDER: S-EPMC4726597 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Single-Nucleotide Polymorphism in ABCC4 Is Associated with Tenofovir-Related Beta2-Microglobulinuria in Thai Patients with HIV-1 Infection.

Likanonsakul Sirirat S Suntisuklappon Bussakorn B Nitiyanontakij Ravee R Prasithsirikul Wisit W Nakayama Emi E EE Shioda Tatsuo T Sangsajja Chariya C

PloS one 20160125 1

<h4>Background</h4>In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected individuals since 2001. Due to relatively frequent adverse effects, d4T gradually has been replaced with tenofovir disoproxil fumarate (TDF). Although the frequency of adverse drug effects with TDF is lower than that with d4T, TDF is known to induce kidney dysfunction, especially in the proximal tubules. It has ...[more]

PMID: 26807589

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Project description:Tenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded by ABCC2 and ABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms of ABCC2 and ABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and the ABCC4 4131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having the ABCC4 4131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.).

Project description:INTRODUCTION:Understanding the current epidemiology of human immunodeficiency virus (HIV) infection in Thailand will facilitate more effective national HIV prevention programs. This study aimed to determine the prevalence and risk factors for HIV infection among young Thai men. METHODS:A total survey was conducted of Royal Thai Army new conscripts, participating in the national HIV surveillance in November 2010 and May 2011. Behavioral risk factors for HIV infection were determined using a standardized survey questionnaire in the total study population and men who have sex with men (MSM) subgroup. RESULTS:A total of 301 (0.5%) HIV infected young Thai men were identified from the total study population (63,667). Independent risk factors associated with HIV infection among the total study population included being single (adjusted Odds Ratio [AOR] 1.6, 95% Confidence Interval [CI] 1.1-2.2), having no formal education (AOR 6.5, 95% CI 2.3-18.4) or a bachelor's degree (AOR 1. 8, 95% CI 1.0-3.0), engaging in bisexual (AOR 3.7, 95% CI 2.4-5. 6) or exclusively homosexual activity (AOR 14.4, 95% CI 10.4-19.8), having a history of Sexually Transmitted Infection (STI) (AOR 2.3, 95% CI 1.6-3.3) and having sex in exchange for gifts/money (AOR 2.0, 95% CI 1. 5-2.8). A total of 4,594 (7.9%) MSM were identified, of which 121 (2.6%) were HIV infected. The prevalence of HIV infection among MSM in urban (2.8%) and rural (2.4%) areas were relatively comparable (p-value = 0.44). Of the identified MSM, 82.5% reported having sexual desire with females only. Risk factors associated with HIV infection in the MSM subgroup included living in the western region (AOR 3.5, 95% CI 1.2-10.4), having a bachelor's degree (AOR 2.7, 95% CI 1.2-5.7), having a history of exclusive receptive (AOR 3.6, 95% CI 1.6-7.7) or versatile anal sex (AOR 4.7, 95% CI 3.0-7.5) and history of having sex in exchange for gifts/money (AOR 2.3, 95% CI 1.5-3.5). CONCLUSION:The prevalence of HIV infection among young Thai men has continued to be below 0.5% in 2010 and 2011. High risk sexual activity, including MSM, played a major role in the HIV epidemic among this population. Effective HIV prevention programs should cover MSM who have heterosexual desire as well as having sex in exchange for gifts/money and be implemented in both urban and rural areas.

Dataset Information

A Single-Nucleotide Polymorphism in ABCC4 Is Associated with Tenofovir-Related Beta2-Microglobulinuria in Thai Patients with HIV-1 Infection.

Publications

A Single-Nucleotide Polymorphism in ABCC4 Is Associated with Tenofovir-Related Beta2-Microglobulinuria in Thai Patients with HIV-1 Infection.

Similar Datasets

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