Clinical perspectives on human genetic screening to prevent nevirapine toxicity.
Clinical perspectives on human genetic screening to prevent nevirapine toxicity.
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DOI：
10.2217/pme.12.82
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发表时间：
2012-09-01
影响因子：
2.3
通讯作者：
Nevirapine Toxicogenomics Study Team
中科院分区：
文献类型：
--
作者：
Haas DW;Mootsikapun P;Ruxrungtham K;Podzamczer D;Nevirapine Toxicogenomics Study Team
奈韦拉平是世界上最广泛使用的抗逆转录病毒药物之一。然而，当CD 4 T细胞计数较高的抗逆转录病毒初治个体开始含奈韦拉平的治疗方案时，严重毒性的风险增加。几种遗传变异与奈韦拉平毒性相关。作者使用先前研究的数据来预测遗传筛查的潜在后果，以预防奈韦拉平不良事件。该研究招募了11个国家的非洲、亚洲和欧洲血统队列，其中包括276名在使用含奈韦拉平方案时经历过严重皮肤和/或肝脏不良事件的患者和587名匹配的奈韦拉平耐受对照组。与HLA-Cw*04、HLA-B*35、HLA-DRB*01和CYP 2B 6 516 G>T（rs3745274）相关;然而，这些遗传标记物的阳性预测值较低，大多数奈韦拉平相关不良事件发生在无这些标记物的患者中。除非确定更好的遗传预测因子，否则避免奈韦拉平毒性的最佳方法是继续遵循目前主要基于CD 4 T细胞标准的处方指南。
Nevirapine is one of the most extensively prescribed antiretroviral drugs worldwide. However, a concern is increased risk for severe toxicity when antiretroviral-naive individuals with higher CD4 T-cell counts initiate nevirapine-containing regimens. Several genetic variants are associated with nevirapine toxicities. The authors used data from a previous study to anticipate potential consequences of genetic screening to prevent nevirapine adverse events. That study enrolled cohorts of African, Asian and European descent in 11 countries, including 276 patients who had experienced severe cutaneous and/or hepatic adverse events with nevirapine-containing regimens and 587 matched nevirapine-tolerant controls. Associations were identified with HLA-Cw*04, HLA-B*35, HLA-DRB*01 and CYP2B6 516G>T (rs3745274); however, positive predictive values for these genetic markers were low, and most nevirapine-associated adverse events occurred in patients without these markers. Unless better genetic predictors are identified, nevirapine toxicity is best avoided by continuing to follow current prescribing guidelines that are based largely on CD4 T-cell criteria.
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