Pharmacogenetics of efavirenz discontinuation for reported central nervous system symptoms appears to differ by race.
Pharmacogenetics of efavirenz discontinuation for reported central nervous system symptoms appears to differ by race.
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Efavirenz停用的中枢神经系统症状的药物遗传学似乎因种族而有所不同。
DOI：
10.1097/fpc.0000000000000238
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发表时间：
2016-10
影响因子：
2.6
通讯作者：
Haas DW
中科院分区：
文献类型：
--
作者：
Leger P;Chirwa S;Turner M;Richardson DM;Baker P;Leonard M;Erdem H;Olson L;Haas DW
依法韦仑经常引起中枢神经系统（CNS）症状。我们评估了在治疗开始后12个月内因CNS症状而停用依法韦仑的遗传相关性。患者在美国东南部的一家HIV初级保健诊所开始了含依法韦仑的治疗方案，并有至少12个月的随访数据。CYP2B6和CYP2A6的多态性定义了依法韦仑代谢物类别。全基因组基因分型允许调整人群分层。在563例可评价的患者中，99例（17.5%）在12个月内停用依法韦仑，29例（5.1%）因CNS症状。慢代谢者与快代谢者因CNS症状而停用依法韦仑的风险比（HR）为4.9（95% CI）。1.9至12.4; p = 0.001）。白人的HR为6.5（95% CI：2.3 - 18.8; p = 0.001），黑人为2.6（95% CI：2.3 - 18.8; p = 0.001）。0.5至14.1; p = 0.27）。仅考虑慢代谢者，白人与黑人的HR为3.1（95% CI：0.9 - 11.0; p = 0.081）。慢代谢基因型对依非韦伦停药的阳性预测值在白人中为27%，在黑人中为11%。慢代谢基因型与因CNS症状而停用依法韦仑显著相关。这种联系在白人中比在黑人中强得多。
Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation. Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the southeastern United States, and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping allowed adjustment for population stratification. Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 (95% C.I. 1.9 to 12.4; p = 0.001). This HR in Whites was 6.5 (95% CI: 2.3 to 18.8; p = 0.001), and in Blacks was 2.6 (95% C.I. 0.5 to 14.1; p = 0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9 to 11.0; p = 0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks. Slow metabolizer genotypes were significantly associated with efavirenz discontinuation for reported CNS symptoms. This association was considerably stronger in Whites than in Blacks.