Leger Paul, Chirwa Sanika, Nwogu Jacinta N, Turner Megan, Richardson Danielle M, Baker Paxton, Leonard Michael, Erdem Husamettin, Olson Lana, Haas David W
Department of Medicine.
Department of Pharmacology.
Pharmacogenet Genomics. 2018 Jan;28(1):1-6. doi: 10.1097/FPC.0000000000000316.
Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity.
Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses.
Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of Black, 21.4% of Hispanic, and 8.6% of White patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 [95% confidence interval (CI): 1.7-31.5; P=0.007]. Among 152 White patients the HR was 14.4 (95% CI: 2.6-78.7; P=0.002), but among 153 Black patients the HR was 0.8 (95% CI: 0.05-12.7; P=0.87).
Among patients who initiated atazanavir/ritonavir-containing regimens, UGT1A1 slow metabolizer genotype rs887829 T/T was associated with increased bilirubin-related discontinuation of atazanavir in White but not in Black patients, this despite T/T genotype being more frequent in Black patients.
阿扎那韦可导致血浆间接胆红素升高。我们评估了吉尔伯特多态性与按种族/族裔分层的胆红素相关阿扎那韦停药之间的关联。
患者在美国东南部一家HIV初级保健诊所开始接受含阿扎那韦/利托那韦的治疗方案，且有至少12个月的随访数据。代谢者组由UGT1A1 rs887829 C→T定义。在合并人群分析中，全基因组基因型数据用于调整遗传血统。
在321例可评估患者中，15例（4.6%）在12个月内出现与胆红素相关的阿扎那韦停药。rs887829 T/T纯合子在28.1%的黑人、21.4%的西班牙裔和8.6%的白人患者中存在。在所有患者中，T/T基因型与C/C基因型相比，胆红素相关停药的风险比（HR）为7.3[95%置信区间（CI）：1.7 - 31.5；P = 0.007]。在152例白人患者中，HR为14.4（95%CI：2.6 - 78.7；P = 0.002），但在153例黑人患者中，HR为0.8（95%CI：0.05 - 12.7；P = 0.87）。
在开始接受含阿扎那韦/利托那韦治疗方案的患者中，UGT1A1慢代谢者基因型rs887829 T/T与白人患者中胆红素相关的阿扎那韦停药增加有关，而在黑人患者中则不然，尽管T/T基因型在黑人患者中更常见。
