Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission
Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission
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DOI：
10.1097/00002030-200007280-00001
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发表时间：
2000-07-28
期刊：
影响因子：
3.8
通讯作者：
Eshleman, SH
中科院分区：
文献类型：
--
作者：
Jackson, JB;Becker-Pergola, G;Eshleman, SH
目的：乌干达最近的一项试验表明，一种简单、廉价的奈韦拉平（NVP）预防方案可以显著降低HIV-1垂直传播风险。在该方案中，妇女在分娩开始时接受单剂量NVP，婴儿在出生后72小时内接受单剂量NVP。本研究的目的是确定在I/II期试验HIVNET 006中接受该方案的乌干达妇女中是否选择了具有NVP耐药突变的HIV-1变异体。方法：分析15名妇女在服用NVP后6周的血浆HIV-1逆转录酶（RT）序列。还分析了NVP给药前收集的血浆RT序列。结果：15名妇女中有3名（20%）在给予NVP 6周后检测到K103N耐药突变（95%置信区间，0-40%）。三名妇女中的两名可获得剂量前样本；两种剂量前样本都没有突变。所有15名女性均未发现其他NVP抗性突变。携带K103N突变的女性比未携带K103N突变的女性有更长的NVP消除半衰期、更低的中位口服清除率和更高的浓度时间曲线下的中位面积。在分娩33个月后，从这三名妇女中的一名获得可评估的样本；在该样本中未检测到K103N突变。结论：这项初步研究表明，在一些乌干达妇女注射单剂量NVP后，可以检测到携带RT K103N突变的HIV-1。这表明，非核苷类RT抑制剂耐药可能在一些人通过单剂量NVP预防选择。药代动力学数据表明，给药后较长时间暴露于NVP可能有利于NVP耐药HIV-1的选择。(C) 2000 Lippincott Williams & Wilkins。
Objective: A recent trial in Uganda demonstrated that a simple, inexpensive regimen of nevirapine (NVP) prophylaxis can dramatically reduce HIV-1 vertical transmission risk. In this regimen, women receive a single dose of NVP at the onset of labor and infants receive a single dose of NVP within 72 h of birth. The objective of this study was to determine whether HIV-1 variants with NVP resistance mutations were selected in Ugandan women who received this regimen in the Phase I/II trial HIVNET 006.Methods: Reverse transcriptase (RT) sequences from plasma HIV-1 were analyzed from 15 women 6 weeks after NVP dosing. RT sequences from plasma collected prior to NVP dosing were also analyzed.Results: The K103N NVP resistance mutation was detected 6 weeks after NVP administration in three (20%) out of 15 women (95% confidence interval, 0-40%). Pre-dose samples were available from two of the three women; both pre-dose samples lacked the mutation. Other NVP resistance mutations were absent from all 15 women. Women with the K103N mutation had a longer median NVP elimination half-life, decreased median oral clearance, and increased median area under the concentration time curve than those without the mutation. An evaluable sample was obtained from one of these three women 33 months after delivery; the K103N mutation was not detected in that sample.Conclusions: This preliminary study demonstrates that HIV-1 with the RT K103N mutation can be detected in some Ugandan women following a single dose of NVP. This suggests that non-nucleoside RT inhibitor resistance may be selected in some people by single dose NVP prophylaxis. Pharmacokinetic data suggested that a more prolonged exposure to NVP after dosing may favor selection of NVP-resistant HIV-1. (C) 2000 Lippincott Williams & Wilkins.