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在急性治疗的艾滋病毒疾病期间,完整和缺陷的艾滋病毒DNA储库的快速双相衰变

Alton Barbehenn¹, Lei Shi², Junzhe Shao²

¹Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco, San Francisco, CA 94110, USA.

medRxiv : the preprint server for health sciences

|April 8, 2024

概括

在艾滋病毒感染者 (PWH) 中早期启动抗逆转录病毒疗法 (ART) 会导致艾滋病毒储存库的衰变更快. 这种数学模型预测了水库衰变,为未来的艾滋病毒治疗策略提供了信息.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
数学生物学数学生物学

背景情况:

抗逆转录病毒疗法 (ART) 抑制HIV复制,但不能从潜伏感染的细胞中消除病毒,形成HIV储存库.
了解艾滋病毒储存库动态对于开发有效的艾滋病毒治愈策略至关重要.
在急性感染期间治疗后,对艾滋病毒储库衰变动力学存在有限的数据.

研究的目的:

开发和验证一个数学模型来预测艾滋病毒储衰变在艾滋病毒感染者 (PWH) 开始ART在急性感染期间.
分析影响艾滋病毒储库衰变率的因素,包括ART启动时间和基线免疫学参数.
提供有关艾滋病毒储库动态早期阶段的见解,以告知治愈干预措施.

主要方法:

使用了来自67个PWH在急性艾滋病毒感染期间接受治疗的500个纵向样本.
开发了一种新的数学模型,使用非线性通用添加模型来预测来自外围CD4+T细胞的储衰变.
在ART的第一年分析完整和缺陷的HIVDNA的衰变率.

主要成果:

在ART的第一年观察到完整的HIVDNA的快速双相衰变 (t1/2~2.83周和~15.4周).
与以前报告的慢性治疗PWH的估计相比,HIV储存库衰变的估计大约是5倍快.
较快的衰变率与早期的ART启动,较高的初始CD4+T细胞数量和较低的ART前病毒载荷有关.

结论:

在急性艾滋病毒感染期间早期启动ART显著加快了艾滋病毒储库衰变.
开发的数学模型提供了一个工具来预测水库衰变,并评估影响它的因素.
这些发现对于优化针对HIV治愈干预措施的时间和策略至关重要.

关键词:

艾滋病毒储库衰变急性艾滋病病毒感染.抗逆转录病毒治疗 (ART)暴露前预防 (PrEP) 是指暴露前预防.

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