Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure
Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure
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DOI：
10.1056/nejmoa1000931
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发表时间：
2010-10-14
影响因子：
158.5
通讯作者：
Violari, Avy
中科院分区：
文献类型：
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作者：
Palumbo, Paul;Lindsey, Jane C.;Violari, Avy
背景：在资源有限的环境中，单剂量奈韦拉平是预防人类免疫缺陷病毒（HIV）母婴传播方案的基础，但奈韦拉平经常选择在预防后仍感染的母亲和儿童中使用耐药病毒。对于先前曾接触过单剂量奈韦拉平的儿童，最佳抗逆转录病毒治疗策略尚不清楚。方法：我们在6个非洲国家进行了一项随机试验，对符合世界卫生组织（who）标准的6 - 36月龄hiv感染儿童进行了齐多夫定和拉米夫定联合奈韦拉平或利托那韦增强型洛匹那韦的初始治疗。结果该队列包括暴露于单剂量奈韦拉平预防的儿童。主要终点是研究第24周时病毒学失败或停止治疗。在数据和安全监测委员会的建议下，该队列的登记被提前终止。结果共纳入164名儿童。CD4+淋巴细胞中位数百分比为19%；共有56%的儿童患有世卫组织第3或第4期疾病。奈韦拉平组比利托那韦增强洛匹那韦组有更多的儿童达到了主要终点（39.6%对21.7%；加权差为18.6个百分点；95%置信区间为3.7到33.6；名义P = 0.02）。148名儿童中有18名（12%）检测到奈韦拉平基线耐药，可预测治疗失败。组间不良事件发生率无显著差异。结论在曾接受单剂量奈韦拉平围产期预防HIV传播的儿童中，齐多夫定和拉米夫定加利托那韦的洛匹那韦抗逆转录病毒治疗效果优于齐多夫定和拉米夫定加奈韦拉平治疗。由于奈韦拉平在资源有限的环境中用于治疗和围产期预防艾滋病毒感染，因此迫切需要预防艾滋病毒母婴传播以及治疗艾滋病毒感染的替代战略。
BACKGROUNDSingle-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown.METHODSWe conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria.RESULTSare reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. Results A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events.CONCLUSIONSAmong children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required.