Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San Francisco, San Francisco, CA, USA.
Department of Biostatistics, University of California Berkeley, Berkeley, CA, USA.
Nat Commun. 2024 Nov 18;15(1):9966. doi: 10.1038/s41467-024-54116-1.
Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t ~ 2.83 weeks; week 5-24: t ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.
尽管进行了抗逆转录病毒疗法（ART），但 HIV 仍存在于潜伏感染的细胞（HIV 储存库）中，这些细胞会随着时间的推移缓慢衰减。在这里，我们利用 67 名急性感染期接受治疗的 HIV 感染者（PLWH）的 >500 个纵向样本，开发了一种数学模型，以从外周血 CD4+T 细胞预测储存库的衰减情况。非线性广义加性模型显示完整 DNA 的快速双相衰减（第 0-5 周：t2.83 周；第 5-24 周：t15.4 周），这种衰减可持续到 1 年。这些估计值比慢性治疗的 PLWH 中之前的衰减估计值快约 5 倍。有缺陷的 DNA 具有类似的双相模式，但数据更具可变性。对于 ART 起始时间更早、初始 CD4+T 细胞计数更高和 ART 前病毒载量更低的 PLWH，预测完整和有缺陷的衰减率更快。在这项研究中，我们在 ART 起始时对 HIV 储存库衰减有了更深入的了解，为针对这一关键时期的未来治疗策略提供了信息。
