Division of Infectious Diseases, Department of Medicine II, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.
Department of Infection Medicine, Medical Service Centre Clotten, Freiburg, Germany.
AIDS Res Ther. 2021 Jun 30;18(1):37. doi: 10.1186/s12981-021-00361-z.
Cytomegalovirus (CMV) infection is one of the main driving forces of T-cell senescence in the general population, whereas its differential impact in people living with HIV (PLWH) is less well characterized. The study explores the effect of latent CMV infection on T-cell subsets, monocyte/macrophages activation markers, and CRP in PLWH on long-term ART.
Cross-sectional cohort study including PLWH on long-term suppressive ART. Individuals of 4 groups (HIV+CMV-, HIV+CMV+, HIV-CMV+, and HIV-CMV-) were matched 1:1:1:1 for age and sex. Immunophenotyping of lymphocyte and T-cell subsets by multicolor flow cytometry was performed in fresh blood samples collected from patients and healthy donors.
Both, latent CMV and treated HIV infection were associated with an expansion of CD8 T cells, a reduced CD4/CD8 ratio, and with CD8 T-cell activation with a cumulative effect in CMV/HIV-coinfected individuals. CMV was associated with elevated numbers of late effector and terminally differentiated CD8 T-cells. Compared to CMV monoinfection, CMV/HIV coinfection showed to be associated with lower proportion of CD28-CD8+ T cells expressing CD57 suggesting that HIV preferentially expands CD28-CD57-CD8+ T cells and impedes terminal differentiation of CD28-CD8+ T cells. We could not show any association between HIV or CMV infection status and concentration of CRP and CD163.
CMV infection is associated with phenotypic signs of T-cell senescence, promoting exacerbation and persistence of alterations of the T-cell compartment in PLWH on effective ART, which are associated with adverse clinical outcomes and may be an attractive target for therapeutic interventions.
巨细胞病毒（CMV）感染是普通人群中 T 细胞衰老的主要驱动因素之一，而其在 HIV 感染者（PLWH）中的差异影响尚未得到很好的描述。本研究探讨了潜伏性 CMV 感染对 PLWH 长期接受抗逆转录病毒治疗（ART）后 T 细胞亚群、单核细胞/巨噬细胞活化标志物和 C 反应蛋白（CRP）的影响。
本研究纳入了长期接受抑制性 ART 的 PLWH 的横断面队列研究。将 HIV+CMV-、HIV+CMV+、HIV-CMV+和 HIV-CMV-的个体按照年龄和性别 1:1:1:1 进行匹配。从患者和健康供者的新鲜血液样本中通过多色流式细胞术进行淋巴细胞和 T 细胞亚群的免疫表型分析。
潜伏性 CMV 和治疗性 HIV 感染均与 CD8 T 细胞扩增、CD4/CD8 比值降低以及 CD8 T 细胞活化有关，在 CMV/HIV 合并感染个体中具有累积效应。CMV 与晚期效应和终末分化 CD8 T 细胞数量增加有关。与 CMV 单感染相比，CMV/HIV 合并感染与表达 CD57 的 CD28-CD8+T 细胞比例降低有关，这表明 HIV 优先扩增 CD28-CD57-CD8+T 细胞，并阻碍 CD28-CD8+T 细胞的终末分化。我们未发现 HIV 或 CMV 感染状态与 CRP 和 CD163 浓度之间存在任何关联。
CMV 感染与 T 细胞衰老的表型特征有关，在接受有效 ART 的 PLWH 中促进 T 细胞池改变的恶化和持续存在，这与不良临床结局相关，可能成为治疗干预的有吸引力的靶点。
