Krebs Shelly J, Ananworanich Jintanat
aUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA bHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Curr Opin HIV AIDS. 2016 Mar;11(2):163-72. doi: 10.1097/COH.0000000000000228.
The purpose of this review is to outline recent data pertaining to mechanisms of immune activation in acute infection and describe new developments that seek to determine if early antiretroviral treatment can mitigate chronic immune activation.
Following the detection of HIV RNA, highly activated CD8 T cells expand and peak approximately 2 weeks following peak viral load whereas levels of proinflammatory soluble markers coincide with a rise in viral load. Immune activation during acute infection is driven by many factors including pyroptosis, replicative capacity of the infecting virus, and loss of Th17 cells within the gut. Early antiretroviral therapy (ART), particularly if initiated in Fiebig I (HIV IgM-), preserved mucosal CD4 T cells, possibly preventing the release of microbial products associated with immune activation. Viral reservoirs were restricted by the early initiation of ART, and heightened systemic immune activation was partially prevented compared with chronic HIV infection. A strong correlation was found between the size of the viral reservoir and cellular immune activation.
The timing of immune activation during acute infection occurs shortly after exposure. Recent studies demonstrated that ART mitigates inflammatory responses, preserves CD4 T cells, and limits reservoir seeding if provided early in acute HIV infection.
本综述旨在概述近期有关急性感染中免疫激活机制的数据，并描述旨在确定早期抗逆转录病毒治疗是否可减轻慢性免疫激活的新进展。
在检测到HIV RNA后，高度活化的CD8 T细胞会扩增，并在病毒载量达到峰值后约2周达到峰值，而促炎可溶性标志物的水平与病毒载量的上升相一致。急性感染期间的免疫激活由多种因素驱动，包括细胞焦亡、感染病毒的复制能力以及肠道内Th17细胞的丧失。早期抗逆转录病毒治疗（ART），特别是在Fiebig I期（HIV IgM阴性）开始治疗时，可保留黏膜CD4 T细胞，可能防止与免疫激活相关的微生物产物释放。早期开始ART可限制病毒储存库，与慢性HIV感染相比，可部分预防全身免疫激活增强。发现病毒储存库的大小与细胞免疫激活之间存在密切相关性。
急性感染期间免疫激活的时间在接触后不久发生。近期研究表明，如果在急性HIV感染早期提供ART，可减轻炎症反应、保留CD4 T细胞并限制储存库播种。
