Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:
Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA.
Annu Rev Pathol. 2022 Jan 24;17:271-294. doi: 10.1146/annurev-pathol-050520-112001. Epub 2021 Nov 4.
Although antiretroviral therapy (ART) can reduce viremia to below the limit of detection and allow persons living with HIV-1 (PLWH) to lead relatively normal lives, viremia rebounds when treatment is interrupted. Rebound reflects viral persistence in a stable latent reservoir in resting CD4 T cells. This reservoir is now recognized as the major barrier to cure and is the focus of intense international research efforts. Strategies to cure HIV-1 infection include interventions to eliminate this reservoir, to prevent viral rebound from the reservoir, or to enhance immune responses such that viral replication is effectively controlled. Here we consider recent developments in understanding the composition of the reservoir and how it can be measured in clinical studies. We also discuss exciting new insights into the in vivo dynamics of the reservoir and the reasons for its remarkable stability. Finally we discuss recent discoveries on the complex processes that govern viral rebound.
虽然抗逆转录病毒疗法(ART)可以将病毒载量降低到检测限以下,并使 HIV-1 感染者(PLWH)过上相对正常的生活,但治疗中断时病毒载量会反弹。反弹反映了静止 CD4 T 细胞中潜伏储存库中病毒的持续存在。这个储存库现在被认为是治愈的主要障碍,也是国际上激烈研究努力的焦点。治愈 HIV-1 感染的策略包括消除该储存库、防止病毒从储存库中反弹,或增强免疫反应,从而有效控制病毒复制。在这里,我们考虑了对储存库组成及其在临床研究中如何进行测量的最新理解。我们还讨论了关于储存库体内动力学的令人兴奋的新见解,以及其惊人稳定性的原因。最后,我们讨论了最近对控制病毒反弹的复杂过程的发现。