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.
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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