T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus.
T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus.
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感染人类免疫缺陷病毒的女性 T 细胞免疫失调和死亡率。
DOI：
10.1093/infdis/jiab433
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Kaplan,Robert
中科院分区：
文献类型：
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作者：
Peters,BrandilynA;Moon,Jee-Young;Hanna,DavidB;Kutsch,Olaf;Fischl,Margaret;Moran,CaitlinA;Adimora,AdaoraA;Gange,Stephen;Roan,NadiaR;Michel,KatherineG;Augenbraun,Michael;Sharma,Anjali;Landay,Alan;Desai,Seema;Kaplan,Robert
在中位13.3年的随访期间，在HIV感染女性中，CD 4 +T细胞的较高活化和耗竭与非HIV相关死亡风险相关，与基线人口统计学、行为、HIV相关、背景适应性免疫失调是人类免疫缺陷病毒（HIV）感染的一个标志，在抗逆转录病毒治疗（ART）。很少有长期的前瞻性研究有相关的适应性免疫功能障碍的死亡率在HIV，特别是在women.MethodsAmong 606名妇女与艾滋病毒在妇女的机构间艾滋病研究，外周血单核细胞收集2002年至2005年进行多参数流式细胞术。根据截至2018年的国家死亡指数确定了根本死亡原因。我们研究了CD 4+和CD 8 + T细胞活化的相关性，（%CD 38 +HLA-DR+），衰老（%CD57+ CD 28-）、衰竭（%PD-1+）和非活化/正常功能（%CD57-CD 28+）与自然原因、HIV相关和非HIV相关的死亡率。在中位数为13.3年的随访期间，100例死亡中，90例为自然原因（53例非HIV相关，37例HIV相关）。CD 4 +T细胞的较高活化和耗竭与自然原因和非HIV相关死亡率的风险相关，校正基线时的年龄、人口统计学、行为、HIV相关和心脏代谢因素。随时间变化的病毒载量和CD 4 + T细胞计数的额外调整并没有减弱这些关联。CD 8 + T细胞标志物与调整基线factors.ConclusionsPersistent CD 4 + T细胞活化和衰竭的任何结果可能会导致过度的长期死亡率风险的妇女与艾滋病毒，独立的艾滋病毒疾病进展。
SummaryIn women with HIV, higher activation and exhaustion of CD4+T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression.BackgroundDysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women.MethodsAmong 606 women with HIV in the Women’s Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+and CD8+T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28–), exhaustion (%PD-1+), and nonactivation/normal function (%CD57–CD28+) with natural-cause, HIV-related, and non-HIV-related mortality.ResultsAt baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+T-cell count did not attenuate these associations. CD8+T-cell markers were not associated with any outcomes adjusting for baseline factors.ConclusionsPersistent CD4+T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.