HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Department of General Internal Medicine, Ghent University Hospital, Ghent, Belgium.
Front Immunol. 2024 Jan 5;14:1337316. doi: 10.3389/fimmu.2023.1337316. eCollection 2023.
Despite the beneficial effects of antiretroviral therapy (ART) initiation during acute HIV infection (AHI), residual immune activation remains a hallmark of treated HIV infection.
Plasma concentrations of 40 mediators were measured longitudinally in 39 early treated participants of a Belgian AHI cohort (HIV+) and in 21 HIV-negative controls (HIV-). We investigated the association of the inflammatory profile with clinical presentation, plasma viral load, immunological parameters, and in-depth characterization of the HIV reservoir.
While levels of most soluble mediators normalized with suppressive ART, we demonstrated the persistence of a pro-inflammatory signature in early treated HIV+ participants in comparison to HIV- controls. Examination of these mediators demonstrated a correlation with their levels during AHI, which seemed to be viremia-driven, and suggested involvement of an activated myeloid compartment, IFN-γ-signaling, and inflammasome-related pathways. Interestingly, some of these pro-inflammatory mediators correlated with a larger reservoir size and slower reservoir decay. In contrast, we also identified soluble mediators which were associated with favorable effects on immunovirological outcomes and reservoir, both during and after AHI.
These data highlight how the persistent pro-inflammatory profile observed in early ART treated individuals is shaped during AHI and is intertwined with viral dynamics.
尽管抗逆转录病毒疗法(ART)在急性 HIV 感染(AHI)期间的启动具有有益效果,但残留的免疫激活仍然是治疗后 HIV 感染的标志。
在比利时 AHI 队列的 39 名早期治疗参与者(HIV+)和 21 名 HIV 阴性对照者(HIV-)中,纵向测量了 40 种介质的血浆浓度。我们研究了炎症特征与临床特征、血浆病毒载量、免疫参数以及 HIV 储存库的深入特征之间的关联。
虽然大多数可溶性介质的水平随着抑制性 ART 而正常化,但我们证明与 HIV-对照者相比,早期治疗的 HIV+参与者中存在持续的促炎特征。对这些介质的检查表明它们与 AHI 期间的水平相关,这似乎是由病毒血症驱动的,并表明激活的髓样细胞区室、IFN-γ 信号和炎症小体相关途径的参与。有趣的是,其中一些促炎介质与较大的储存库大小和较慢的储存库衰减相关。相比之下,我们还确定了与免疫病毒学结果和储存库在 AHI 期间和之后都相关的有利影响的可溶性介质。
这些数据强调了在早期 ART 治疗个体中观察到的持续的促炎特征是如何在 AHI 期间形成的,并且与病毒动力学交织在一起。