Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, New South Wales, Australia.
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Nat Rev Immunol. 2019 Jan;19(1):45-54. doi: 10.1038/s41577-018-0085-4.
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.
正在探索各种干预措施以诱导 HIV 的功能性治愈，其目的是让患者能够长时间甚至终身停止抗逆转录病毒治疗（ART）。这些干预措施都旨在诱导 HIV 发病和疾病进展的无 ART 缓解，但实现这一目标的方式却截然不同，包括减少潜伏储存库的大小（例如，小分子刺激潜伏感染细胞）、减少可供病毒利用的靶细胞数量（例如，基因治疗）或改善免疫反应（例如，主动或被动免疫疗法）。在这里，我们考虑了一些用于诱导治疗后 HIV 控制的替代策略，并使用数学模型来预测这些不同方法所固有的挑战的规模。对于许多方法，需要超过 99.9%的功效才能诱导持久的无 ART 缓解。目前，个别方法的功效远低于我们预测所需的水平，需要新的技术来实现终身功能性治愈。
