Antiretroviral drugs for preventing mother-to-child transmission of HIV in sub-Saharan Africa: balancing efficacy and infant toxicity
Antiretroviral drugs for preventing mother-to-child transmission of HIV in sub-Saharan Africa: balancing efficacy and infant toxicity
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DOI：
10.1097/qad.0b013e3283189bd7
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发表时间：
2008-11-12
期刊：
影响因子：
3.8
通讯作者：
Walensky, Rochelle P.
中科院分区：
文献类型：
--
作者：
Ciaranello, Andrea L.;Seage, George R., III;Walensky, Rochelle P.
目的：抗逆转录病毒药物可预防HIV感染母婴传播，但宫内暴露可能与线粒体毒性引起的神经系统症状有关。我们试图确定目前推荐的预防母婴传播的方案，以最佳地平衡儿童艾滋病毒感染和神经线粒体毒性的风险。设计：将已发表的MTCT和线粒体毒性数据用于撒哈拉以南非洲妇女MTCT的决策分析模型。方法：我们调查了未进行抗逆转录病毒预防的HIV和线粒体毒性风险，以及从单剂奈韦拉平到三药抗逆转录病毒疗法(ART)的五种推荐方案。敏感性分析改变了所有参数，包括婴儿喂养策略和相对于艾滋病毒的线粒体毒性的丧失。结果：不提供抗逆转录病毒药物是最不有效和毒性最小的策略，18个月的HIV风险为30.4%，线粒体毒性风险为0.2%(母乳喂养的婴儿)。随着用药次数和用药时间的增加，HIV风险显著降低(三药ART组降至4.9%)，但线粒体毒性风险也增加(2.2%，三药ART组也是如此)。尽管毒性增加，但三种药物ART将总的不良儿童结局(艾滋病毒加线粒体毒性)降至最低，除非已公布的艾滋病毒和线粒体毒性的最高风险为真，或者线粒体毒性的残疾超过艾滋病毒感染的6.4倍。结论：有效的预防母婴传播的方案导致儿童线粒体毒性的风险至少比效果较差的方案导致的艾滋病毒感染风险低一个数量级。对线粒体毒性的担忧目前不应限制三药联合抗逆转录病毒疗法的使用，以防止母婴传播。(C)2008年Wolters Kluwer Health|Lippincott Williams&Wilkins
Objective: Antiretroviral drugs can prevent mother-to-child transmission of HIV infection, but in-utero antiretroviral exposure may be associated with neurologic symptoms due to mitochondrial toxicity. We sought to identify the currently recommended regimen to prevent mother-to-child transmission that optimally balances risks of pediatric HIV infection and neurologic mitochondrial toxicity.Design: Published MTCT and mitochondrial toxicity data were used in a decision analytic model of MTCT among women in sub-Saharan Africa.Methods: We investigated the HIV and mitochondrial toxicity risks associated with no antiretroviral prophylaxis and five recommended regimens ranging from single-dose nevirapine to three-drug antiretroviral therapy (ART). Sensitivity analyses varied all parameters, including infant feeding strategy and the disability of mitochondrial toxicity relative to HIV. Results: Provision of no antiretroviral drugs is the least effective and least toxic strategy, with 18-month HIV risk of 30.4% and mitochondrial toxicity risk of 0.2% (breastfed infants). With increasing drug number and duration, HIV risk decreases markedly (to 4.9% with three-drug ART), but mitochondrial toxicity risk also increases (to 2.2%, also with three-drug ART). Despite increased toxicity, three-drug ART minimizes total adverse pediatric outcomes (HIV plus mitochondrial toxicity), unless the highest published risks are true for both HIV and mitochondrial toxicity, or the disability from mitochondrial toxicity exceeds 6.4 times that of HIV infection.Conclusion: The risk of pediatric mitochondrial toxicity from effective regimens to prevent mother-to-child transmission is at least an order of magnitude lower than the risk of HIV infection associated with less-effective regimens. Concern regarding mitochondrial toxicity should not currently limit the use of three-drug ART to prevent mother-to-child transmission where it is available. (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins