围产期接触奈韦拉平的儿童的抗逆转录病毒治疗。

Antiretroviral treatment for children with peripartum nevirapine exposure.

机构信息

Department of Medicine, Dartmouth Medical School, Lebanon, NH 03765, USA.

出版信息

N Engl J Med. 2010 Oct 14;363(16):1510-20. doi: 10.1056/NEJMoa1000931.

DOI:10.1056/NEJMoa1000931

PMID:20942667

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3021781/

Abstract

BACKGROUND

Single-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.

METHODS

We 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. Results are 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.

CONCLUSIONS

Among 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. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.).

摘要

背景

在资源有限的环境中，单剂量奈韦拉平是预防母婴传播人类免疫缺陷病毒（HIV）方案的基石，但奈韦拉平经常会选择那些尽管接受了预防措施但仍感染的母亲和儿童中的耐药病毒。对于曾接触过单剂量奈韦拉平的儿童，最佳的抗逆转录病毒治疗策略尚不清楚。

方法

我们在六个非洲国家开展了一项随机试验，纳入了符合世界卫生组织（WHO）标准的 6 至 36 个月龄、已感染 HIV 的儿童，对其进行初始治疗，治疗方案为齐多夫定和拉米夫定联合奈韦拉平或利托那韦增效洛匹那韦。本文报告了包括曾接受单剂量奈韦拉平预防的儿童的队列结果。主要终点为研究第 24 周时病毒学失败或治疗终止。根据数据和安全监测委员会的建议，提前终止了该队列的入组。

结果

共有 164 名儿童入组。CD4+淋巴细胞中位数为 19%；56%的儿童患有 WHO 分期 3 或 4 期疾病。奈韦拉平组达到主要终点的儿童多于利托那韦增效洛匹那韦组（39.6%比 21.7%；加权差异，18.6 个百分点；95%置信区间，3.7 至 33.6；名义 P=0.02）。148 名儿童中有 18 名（12%）基线时对奈韦拉平耐药，耐药预测治疗失败。两组间不良事件发生率无显著差异。

结论

对于曾接受单剂量奈韦拉平预防围产期母婴 HIV 传播的儿童，齐多夫定和拉米夫定联合利托那韦增效洛匹那韦的抗逆转录病毒治疗方案的结果优于齐多夫定和拉米夫定联合奈韦拉平的治疗方案。由于奈韦拉平在资源有限的环境中既用于 HIV 感染的治疗，也用于母婴 HIV 感染的预防，因此迫切需要替代策略来预防母婴 HIV 传播，并治疗 HIV 感染。（由美国国立卫生研究院资助；临床试验.gov 编号，NCT00307151）。