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长达12周的加兰他并没有改善ART抑制的HIV感染者的神经认知或免疫激活

Anjana Yadav¹, Alisa J Stephens-Shields², Antoneta Karaj²

¹Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

AIDS (London, England)

|December 22, 2025

概括

在接受ART治疗的HIV患者中,无论吸烟状况如何,Galantamine都没有改善神经认知或减少炎症. 这项研究发现,在这个脆弱人群中,对认知功能或炎症标志物没有显著的益处.

科学领域:

神经科学是一个神经科学.
免疫学免疫学免疫学
传染性疾病传染性疾病

背景情况:

接受抗逆转录病毒疗法 (ART) 的艾滋病毒感染者 (PWH) 患有高比例的非艾滋病相关并发症,包括与艾滋病毒相关的神经认知障碍.
持续的单细胞/巨细胞激活有助于PWH的神经炎症和认知障碍.
吸烟加剧PWH的并发症,但尼古丁通过α7-尼古丁性乙胆受体 (α7-nAChR) 激活表现出抗炎性质.

研究的目的:

研究α7-nAChR增强剂兰胺 (GAL) 在改善神经认知和减少PWH/ART患者炎症方面的疗效.
探讨GAL的影响在吸烟者和非吸烟者之间是否有所不同.
评估GAL对单细胞和T细胞激活标记物以及血炎症调解物的影响.

主要方法:

一项为期12周的双盲,随机,安慰剂控制的交叉研究,涉及吸烟者和非吸烟者PWH/ART.
主要结局包括复合神经认知评分,单细胞和CD8T细胞激活标记 (例如CD16,CD163,CCR2,CD38,HLA-DR) 和血生物标记 (例如sCD163,CCL2).
探索性分析使用了Luminex测定用于血介质和RNAseq用于单细胞转录组.

主要成果:

与安慰剂相比,Galantamine治疗没有显著改善复合神经认知测试得分 (p=0.82),没有根据吸烟状态观察到差异 (p=0.51).
单细胞CCR2表达与GAL显著增加 (p=0.006),但其他免疫标记物 (单细胞CD16,CD163;CD8T细胞CD38/HLA-DR) 和血生物标记物 (sCD163,CCL2) 没有显著变化.
血神经纤维光链 (NFL) 和高灵敏性C反应蛋白 (hsCRP) 保持不变;然而,几种促炎细胞因子随着GL治疗而增加,单细胞基因表达仅表现出适度的影响.

结论:

经过12周的加兰他治疗,在接受ART治疗的HIV患者中未能显示出认知或抗炎功效.
研究结果表明,在这种人群中,GAL不是治疗艾滋病毒相关的神经认知障碍或全身炎症的有效干预措施.
吸烟状态并没有改变加兰他胺在改善神经认知或减少PWH/ART中的炎症方面的缺乏有效性.

关键词:

盖兰他胺是一种胺.他们的手握手.艾滋病毒并发症艾滋病毒并发症一个单细胞单细胞.尼古丁是一种尼古丁.剩余的炎症剩余的炎症烟草烟草烟草烟草烟草

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