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反映胸腺功能保留的生物标志物谱与老年HIV感染者合并症减少相关:一项AGEhIV队列分析。

A Biomarker Profile Reflective of Preserved Thymic Function Is Associated With Reduced Comorbidities in Aging People With HIV: An AGEhIV Cohort Analysis.

作者信息

Vanbellinghen Manon C, Boyd Anders, Kootstra Neeltje A, Schim van der Loeff Maarten F, van der Valk Marc, Reiss Peter

机构信息

Department of Infectious Diseases, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands.

出版信息

J Infect Dis. 2025 Mar 17;231(3):622-632. doi: 10.1093/infdis/jiae603.

Abstract

BACKGROUND

People with HIV (PWH) experience a higher burden of aging-associated comorbidities, the underlying mechanisms of which remain to be fully elucidated. We aimed to identify profiles based on immune, inflammatory, and aging biomarkers in blood from PWH and controls, and explore their association with total comorbidities over time.

METHODS

Latent profile analysis was used to construct biomarker profiles in AGEhIV cohort participants (94 with well-controlled HIV on antiretroviral therapy [ART] and 95 controls without HIV) using baseline measurements of selected biomarkers. Factors associated with profile membership were assessed by multivariable logistic regression. The association between profiles and mean total comorbidities during follow-up was assessed by Poisson regression, stratified by HIV status. Comorbidities included type 2 diabetes, non-AIDS malignancies, cardiovascular disease, osteoporosis, chronic kidney disease. and frailty.

RESULTS

Three biomarker profiles were identified: "high thymic output/low inflammation" (HT/LI) profile (n = 27 PWH, n = 9 controls), "low thymic output/high inflammation" (LT/HI) profile (n = 29 PWH, n = 26 controls), and an "intermediate" profile (n = 38 PWH, n = 60 controls). Only HIV status was significantly associated with profile membership. PWH, relative to controls, more often exhibited the HT/LI profile compared to other profiles. In PWH, but not in controls, the HT/LI profile was associated with significantly lower mean comorbidities during a median 8.0 years (interquartile range, 7.1-8.1) of follow-up.

CONCLUSIONS

People aging with well-controlled HIV on ART were more likely to exhibit a biomarker profile indicative of preserved thymic function and less chronic inflammation compared to controls. PWH with such a profile seemed relatively protected from developing aging-associated comorbidities.

CLINICAL TRIALS REGISTRATION

NCT01466582.

摘要

背景

人类免疫缺陷病毒感染者(PWH)面临与衰老相关的合并症负担更高,其潜在机制仍有待充分阐明。我们旨在根据PWH和对照组血液中的免疫、炎症和衰老生物标志物确定特征,并探讨它们随时间与总合并症的关联。

方法

使用潜在类别分析,利用选定生物标志物的基线测量值,在AGEhIV队列参与者(94例接受抗逆转录病毒治疗[ART]且HIV得到良好控制者和95例未感染HIV的对照组)中构建生物标志物特征。通过多变量逻辑回归评估与特征归属相关的因素。通过泊松回归评估特征与随访期间平均总合并症之间的关联,并按HIV状态分层。合并症包括2型糖尿病、非艾滋病相关恶性肿瘤、心血管疾病、骨质疏松症、慢性肾脏病和虚弱。

结果

确定了三种生物标志物特征:“高胸腺输出/低炎症”(HT/LI)特征(27例PWH,9例对照组)、“低胸腺输出/高炎症”(LT/HI)特征(29例PWH,26例对照组)和“中间”特征(38例PWH,60例对照组)。仅HIV状态与特征归属显著相关。与对照组相比,PWH与其他特征相比更常表现出HT/LI特征。在PWH中,但在对照组中未发现,HT/LI特征与中位8.0年(四分位间距,7.1 - 8.1)随访期间显著更低的平均合并症相关。

结论

与对照组相比,接受ART且HIV得到良好控制的老年PWH更有可能表现出指示胸腺功能保留和慢性炎症较少的生物标志物特征。具有这种特征的PWH似乎相对不易发生与衰老相关的合并症。

临床试验注册

NCT01466582。

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