研究动态
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HIV 感染和抗逆转录病毒治疗对全身免疫激活生物标志物影响的观察性研究。

Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.

发表日期:2024
作者: Ewelina Kosmider, Jackson Wallner, Ana Gervassi, Rachel A Bender Ignacio, Delia Pinto-Santini, German Gornalusse, Urvashi Pandey, Florian Hladik, Paul T Edlefsen, Javier R Lama, Ann C Duerr, Lisa M Frenkel
来源: Immunity & Ageing

摘要:

评估全身性炎症的生物标志物是否与 HIV 感染或与男性发生性关系的男性开始 ART 的时间(诊断时“立即”,与诊断后 24 周“推迟”)相关。针对男性(MSM)和跨性别女性,我们进行了一项回顾性研究,比较了感染前和 ≥2 年有效 ART 后收集的参与者标本中的炎症生物标志物。我们测量了四份纵向收集的血浆中的生物标志物,其中包括从每位参与者在感染 HIV 之前和之后收集的两份样本,并证实了 ART 抑制。通过酶联免疫测定或 Meso Scale Discovery 对生物标志物进行定量。当评估这些标记物随时间的系统变化时,我们发现参与者的两个感染前或两个 ART 抑制后样本中的多个生物标记物始终存在变化。此外,我们还比较了 HIV 感染前后生物标志物的变化。在 47 名参与者中,C 反应蛋白 (CRP)、单核细胞趋化蛋白 1、肿瘤坏死因子 α 和干扰素 γ 诱导蛋白 10 的水平显着升高,而瘦素和脂多糖结合蛋白 (LBP) 的水平显着降低艾滋病毒感染。随机化延迟 ART 启动与 CRP 的更大增加相关,但 LBP 没有降低。感染艾滋病毒似乎会诱发全身炎症,导致先前与感染和心血管疾病相关的生物标志物升高。与 HIV 诊断后约 24 周延迟 ART 相比,在感染最初几周开始 ART 可以缓和促炎生物标志物的增加。这些发现提供了对立即 ART 启动改善健康结果的潜在介质的深入了解,这可能是因为立即 ART 限制了 HIV 储存库的大小或限制了免疫失调,从而引发了全身炎症。版权所有:© 2024 Kosmider 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. When evaluating systematic variation in these markers over time, we found that multiple biomarkers consistently varied across participants' two pre-infection or two post-ART-suppression specimens. Additionally, we compared changes in biomarkers after vs before HIV acquisition. Across 47 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decrease in LBP. Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to delaying ART for ~24 weeks after HIV diagnosis. These findings provide insight into potential mediators by which immediate-ART initiation improves health outcomes, perhaps because immediate-ART limits the size of the HIV reservoir or limits immune dysregulation that in turn trigger systemic inflammation.Copyright: © 2024 Kosmider et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.