Department of Medicine, Section of Infectious Diseases, Yale University, School of Medicine, New Haven, CT.
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, CA.
J Acquir Immune Defic Syndr. 2018 Mar 1;77(3):337-344. doi: 10.1097/QAI.0000000000001595.
Despite major progress in controlling HIV disease through antiretroviral therapy, changes in immune phenotype and function persist in individuals with chronic HIV, raising questions about accelerated aging of the immune system.
We conducted a cross-sectional study (2005-2007) of HIV-infected (n = 111) and uninfected (n = 114) men from the Veterans Aging Cohort Study. All HIV-infected subjects were on antiretroviral therapy with VL <400 copies/mL for at least 3 years. T-cell markers were examined using flow cytometry. We evaluated the impact of HIV serostatus and age on T-cell phenotypes (expressed as percentages of the total CD4 and CD8 T-cell population) using multivariate linear regression, adjusted for smoking, alcohol, and race/ethnicity. We tested for interactions between HIV and age by including interaction terms.
Among both HIV-infected and uninfected subjects, increasing age was associated with a decreased proportion of naive CD4 T cells (P = 0.014) and CD8 T cells (P < 0.0001). Both HIV infection and increasing age were associated with higher proportions of effector memory CD4 T cells (P < 0.0001 for HIV; P = 0.04 for age) and CD8 T cells (P = 0.0001 for HIV; P = 0.0004 for age). HIV infection, but not age, was associated with a higher proportion of activated CD8 T cells (P < 0.0001). For all T-cell subsets tested, there were no significant interactions between HIV infection and age.
Age and HIV status independently altered the immune system, but we found no conclusive evidence that HIV infection and advancing age synergistically result in accelerated changes in age-associated T-cell markers among virally suppressed individuals.
尽管通过抗逆转录病毒疗法在控制 HIV 疾病方面取得了重大进展,但慢性 HIV 感染者的免疫表型和功能仍会发生变化,这引发了关于免疫系统加速衰老的问题。
我们进行了一项横断面研究(2005-2007 年),纳入了退伍军人老龄化队列研究中的 111 名 HIV 感染者和 114 名未感染者。所有 HIV 感染者均接受抗逆转录病毒治疗,病毒载量(VL)<400 拷贝/毫升,且治疗时间至少 3 年。使用流式细胞术检测 T 细胞标志物。我们使用多元线性回归,调整了吸烟、饮酒和种族/民族等因素,评估了 HIV 感染状况和年龄对 T 细胞表型(以总 CD4 和 CD8 T 细胞群体的百分比表示)的影响,并通过包含交互项来检测 HIV 和年龄之间的交互作用。
在 HIV 感染者和未感染者中,年龄的增长与幼稚 CD4 T 细胞(P = 0.014)和 CD8 T 细胞(P < 0.0001)的比例降低有关。HIV 感染和年龄的增长均与效应记忆 CD4 T 细胞(HIV 相关:P < 0.0001;年龄相关:P = 0.04)和 CD8 T 细胞(HIV 相关:P = 0.0001;年龄相关:P = 0.0004)的比例增加有关。HIV 感染,但不是年龄,与激活的 CD8 T 细胞的比例增加有关(P < 0.0001)。在所有测试的 T 细胞亚群中,HIV 感染和年龄之间没有显著的相互作用。
年龄和 HIV 状态独立地改变了免疫系统,但我们没有确凿的证据表明 HIV 感染和年龄的增长会协同导致病毒抑制个体中与年龄相关的 T 细胞标志物加速变化。