Emerging strategies to deplete the HIV reservoir.
Emerging strategies to deplete the HIV reservoir.
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DOI：
10.1097/qco.0000000000000026
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发表时间：
2014-02
影响因子：
3.9
通讯作者：
Margolis DM
中科院分区：
文献类型：
--
作者：
Archin NM;Margolis DM
这篇综述重点介绍了为进一步推进寻找根除艾滋病毒感染的成功方法而进行的近期研究。
小分子药物化合物，如组蛋白去乙酰化酶抑制剂、含溴结构域和额外末端蛋白（如JQ1）的抑制剂，以及蛋白激酶C激活剂（如苔藓虫素和普罗司他丁），被提议作为在所谓的“激活并杀灭”或“诱导并杀灭”艾滋病毒根除策略中诱导潜伏艾滋病毒表达的潜在候选药物。然而，为了实现病毒清除，人们认为这些化合物可能必须与在成功接受抗逆转录病毒治疗（ART）后长期无病毒血症的患者中增强清除病毒感染细胞的策略协同使用。为此目的的几种候选疗法已经出现，比如治疗性艾滋病毒疫苗——近期临床研究表明，在中断抗逆转录病毒治疗后，它能促进强烈的细胞毒性T细胞反应并抑制病毒反弹。在感染早期接受治疗的艾滋病毒感染者可能是测试这些策略的早期研究的理想对象，因为早期抗逆转录病毒治疗已被证明可限制艾滋病毒储存库的建立。
艾滋病毒潜伏是多因素的，因此根除艾滋病毒感染可能需要多种方法。采用药物学方法针对艾滋病毒潜伏的转化研究工作应同时评估增强艾滋病毒感染者免疫反应以及通过早期抗逆转录病毒治疗限制储存库大小的额外潜在益处。
This review highlights recent studies undertaken to further advance the search for successful approaches to eradicate HIV infection. Small pharmacological compounds such as histone deacetylase inhibitors, inhibitors of bromodomain and extraterminal proteins such as JQ1, and protein kinase C activators such as bryostatin and prostratin are proposed as putative candidates for inducing the expression of latent HIV in a so-called ‘shock and kill’ or ‘kick and kill’ strategy for HIV eradication. However, in order to achieve viral clearance, it is thought likely these compounds will have to be administered in concert with strategies that augment clearance of virus-infected cells in patients that have long been aviremic on successful antiretroviral therapy (ART). Several candidate therapies for this purpose are at hand, such as therapeutic HIV vaccines – recently shown to promote robust cytotoxic T cell responses and blunt viral rebound after ART interruption in clinical studies. HIV-infected patients treated during early infection may be ideal candidates for early studies to test these strategies, as early ART has been shown to limit the establishment of an HIV reservoir. HIV latency is multifactorial and thus the eradication of HIV infection may require multiple approaches. Translational efforts employing pharmacological methods to target HIV latency should evaluate in parallel the additional potential benefits of invigorating the immune response of HIV-infected individuals, and limiting the size of the reservoir via early ART.