Institute for Human Genetics, CNRS, Montpellier, France.
Infectious Diseases Department, Montpellier University Hospital, Montpellier, France.
Front Immunol. 2021 Mar 30;12:663843. doi: 10.3389/fimmu.2021.663843. eCollection 2021.
Chronic immune activation persists in persons living with HIV-1 even though they are aviremic under antiretroviral therapy, and fuels comorbidities. In previous studies, we have revealed that virologic responders present distinct profiles of immune activation, and that one of these profiles is related to microbial translocation. In the present work, we tested in 140 HIV-1-infected adults under efficient treatment for a mean duration of eight years whether low-level viremia might be another cause of immune activation. We observed that the frequency of viremia between 1 and 20 HIV-1 RNA copies/mL (39.5 ± 24.7% versus 21.1 ± 22.5%, p = 0.033) and transient viremia above 20 HIV-1 RNA copies/mL (15.1 ± 16.9% versus 3.3 ± 7.2%, p = 0.005) over the 2 last years was higher in patients with one profile of immune activation, Profile E, than in the other patients. Profile E, which is different from the profile related to microbial translocation with frequent CD38+ CD8+ T cells, is characterized by a high level of CD4+ T cell (cell surface expression of CD38), monocyte (plasma concentration of soluble CD14), and endothelium (plasma concentration of soluble Endothelial Protein C Receptor) activation, whereas the other profiles presented low CD4:CD8 ratio, elevated proportions of central memory CD8+ T cells or HLA-DR+ CD4+ T cells, respectively. Our data reinforce the hypothesis that various etiological factors shape the form of the immune activation in virologic responders, resulting in specific profiles. Given the type of immune activation of Profile E, a potential causal link between low-level viremia and atherosclerosis should be investigated.
慢性免疫激活在接受抗逆转录病毒治疗的 HIV-1 感染者中持续存在，即使他们的病毒载量处于检测不到的水平，这种激活会引发合并症。在之前的研究中，我们已经揭示了病毒学应答者存在不同的免疫激活特征，其中一种特征与微生物易位有关。在本研究中，我们对 140 名接受高效治疗的 HIV-1 感染成人进行了检测，他们的治疗时间平均为八年，以确定低水平病毒血症是否是免疫激活的另一个原因。我们观察到，在过去两年中，病毒载量在 1 至 20 HIV-1 RNA 拷贝/ml（39.5 ± 24.7%比 21.1 ± 22.5%，p = 0.033）和病毒载量短暂超过 20 HIV-1 RNA 拷贝/ml（15.1 ± 16.9%比 3.3 ± 7.2%，p = 0.005）的频率在具有一种免疫激活特征（E 型）的患者中高于其他患者。E 型不同于与频繁 CD38+CD8+T 细胞相关的微生物易位相关特征，其特征是高水平的 CD4+T 细胞（CD38 细胞表面表达）、单核细胞（可溶性 CD14 血浆浓度）和内皮细胞（可溶性内皮蛋白 C 受体血浆浓度）激活，而其他特征则表现为低 CD4:CD8 比值、升高的中央记忆 CD8+T 细胞或 HLA-DR+CD4+T 细胞比例。我们的数据强化了这样一种假设，即各种病因因素塑造了病毒学应答者的免疫激活形式，导致出现特定的特征。鉴于 E 型特征的免疫激活类型，应该研究低水平病毒血症与动脉粥样硬化之间的潜在因果关系。
