Functional cure of HIV: the scale of the challenge
Functional cure of HIV: the scale of the challenge
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DOI：
10.1038/s41577-018-0085-4
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发表时间：
2019-01-01
影响因子：
100.3
通讯作者：
Kent, Stephen J.
中科院分区：
文献类型：
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作者：
Davenport, Miles P.;Khoury, David S.;Kent, Stephen J.
目前正在探索各种干预措施，以诱导艾滋病毒的功能性治愈，目的是使患者能够长期或终身停止抗逆转录病毒疗法。这些干预措施的共同目标是诱导艾滋病毒发病机制和疾病进展的无ART缓解，但以完全不同的方式实现这一目标，通过减少潜伏库的大小（例如，潜伏感染细胞的小分子刺激），减少病毒可用的靶细胞数量（例如，基因治疗）或改善免疫反应（例如，主动或被动免疫治疗）。在这里，我们考虑了一些这些替代策略诱导治疗后控制艾滋病毒和使用数学建模来预测这些不同的方法中固有的挑战的规模。对于许多方法，可能需要超过99.9%的疗效才能诱导持久的无ART缓解。目前，个别方法的疗效远远低于我们预测的必要性，需要新技术来实现终身功能性治疗。
A variety of interventions to induce a functional cure of HIV are being explored, with the aim being to allow patients to cease antiretroviral therapy (ART) for prolonged periods of time or for life. These interventions share the goal of inducing ART-free remission from HIV pathogenesis and disease progression but achieve this in quite different ways, by reducing the size of the latent reservoir (for example, small-molecule stimulation of latently infected cells), reducing the number of target cells available for the virus (for example, gene therapy) or improving immune responses (for example, active or passive immunotherapy). Here, we consider a number of these alternative strategies for inducing post-treatment control of HIV and use mathematical modelling to predict the scale of the challenge inherent in these different approaches. For many approaches, over 99.9% efficacy will likely be required to induce durable ART-free remissions. The efficacy of individual approaches is currently far below what we predict will be necessary, and new technologies to achieve lifelong functional cure are needed.