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UGT1A1 吉尔伯特变异对 AIDS 临床试验组研究 A5202 中利托那韦增效阿扎那韦停药的影响。

Impact of UGT1A1 Gilbert variant on discontinuation of ritonavir-boosted atazanavir in AIDS Clinical Trials Group Study A5202.

机构信息

Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA.

出版信息

J Infect Dis. 2013 Feb 1;207(3):420-5. doi: 10.1093/infdis/jis690. Epub 2012 Nov 12.

DOI:10.1093/infdis/jis690
PMID:23148286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3537445/
Abstract

The UGT1A1*28 variant has been associated with hyperbilirubinemia and atazanavir discontinuation. Protocol A5202 randomly assigned human immunodeficiency virus type 1 (HIV-1)-infected patients to receive atazanavir/ritonavir (atazanavir/r) or efavirenz, with tenofovir/emtricitabine or abacavir/lamivudine. A total of 646 atazanavir/r recipients were evaluable for UGT1A1. Homozygosity for *28/*28 was present in 8% of whites, 24% of blacks, and 18% of Hispanics and was associated with increased bilirubin concentrations. There was an association between 28/28 and increased atazanavir/r discontinuation among Hispanic participants (P = .005) but not among white or black participants (P = .79 and P = .46, respectively). The positive predictive value of 28/28 for atazanavir/r discontinuation among Hispanic participants was only 32% (95% confidence interval, 16%-52%).

摘要

UGT1A128 变异体与高胆红素血症和阿扎那韦停药有关。A5202 方案将人类免疫缺陷病毒 1 型(HIV-1)感染患者随机分配接受阿扎那韦/利托那韦(阿扎那韦/r)或依法韦仑,同时给予替诺福韦/恩曲他滨或阿巴卡韦/拉米夫定。共有 646 名阿扎那韦/r 接受者可评估 UGT1A1。白人、黑人、西班牙裔中 8%、24%和 18%为纯合子28/*28,与胆红素浓度升高有关。在西班牙裔参与者中,28/28 与阿扎那韦/r 停药增加相关(P =.005),但在白人和黑人参与者中无此相关性(P =.79 和 P =.46)。在西班牙裔参与者中,28/28 对阿扎那韦/r 停药的阳性预测值仅为 32%(95%置信区间,16%-52%)。

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