Centre Hospitalier de l'Université de Montréal (CRCHUM).
Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
AIDS. 2018 Jan 28;32(3):293-298. doi: 10.1097/QAD.0000000000001695.
In the quest to eliminate or reduce the HIV reservoir, shock and kill strategies require the combined administration of a latency reversing agent (LRA) to reactivate the latent reservoir and an intervention to boost effector functions to clear this reservoir. Both parts of this strategy are quite inefficient when LRAs are administered to HIV-infected individuals on suppressive ART for several years, possibly due to low levels of induced antigen expression, negative impact of LRAs on clearance mechanisms, and very low number of effective cytotoxic T cells (CTLs). Here we provide rationale for an approach that would require only the administration of an LRA at the time of ART initiation to significantly reduce the HIV reservoir. The advantage of this strategy is an efficient reactivation of the latent HIV reservoir when high numbers of HIV-specific CD8 T cells are present. This strategy may also potentiate more effective CTL responses and the establishment of a longer period of immune surveillance. This “window of opportunity” has been validated , can be tested in preclinical non-human primate (NHP) models and translated rapidly in the clinic.
在消除或减少 HIV 储存库的过程中，冲击和杀伤策略需要联合使用潜伏逆转剂 (LRA) 来重新激活潜伏储存库，并使用干预措施来增强清除该储存库的效应功能。当潜伏逆转剂被用于接受抑制性 ART 治疗多年的 HIV 感染者时，这两种策略都非常低效，这可能是由于诱导的抗原表达水平低、LRA 对清除机制的负面影响以及有效的细胞毒性 T 细胞 (CTL) 数量非常少。在这里，我们提供了一种方法的基本原理，该方法只需在开始 ART 时使用 LRA，即可显著减少 HIV 储存库。这种策略的优势是，当存在大量 HIV 特异性 CD8 T 细胞时，能够有效地重新激活潜伏的 HIV 储存库。这种策略还可能增强更有效的 CTL 反应，并建立更长时间的免疫监测。这个“机会之窗”已经得到了验证，可以在临床前非人类灵长类动物 (NHP) 模型中进行测试，并迅速在临床上转化。
