Piecewise HIV virus dynamic model with CD4(+) T cell count-guided therapy: I.
Piecewise HIV virus dynamic model with CD4(+) T cell count-guided therapy: I.
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DOI：
10.1016/j.jtbi.2012.05.022
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发表时间：
2012-09-07
影响因子：
2
通讯作者：
Wu, Hulin
中科院分区：
文献类型：
--
作者：
Tang, Sanyi;Xiao, Yanni;Wang, Ning;Wu, Hulin
关键词：
抗逆转录病毒治疗的结构性中断（STIs）策略已被提出用于HIV感染者的临床管理，但STIs的临床研究未能得出一致的结论。为了评估STI策略，特别是CD 4 + T细胞计数引导的STI，并解释这些有争议的结论，从不同的临床研究，在本文中，我们提出了使用分段HIV病毒动力学模型定量探索STI策略，并研究其动态行为。我们的分析结果表明，CD 4 + T细胞计数可以保持在一个安全的水平以上，使用STI与一个单一的阈值或阈值窗口。数值模拟表明，根据规定的上限或下限阈值，患者的CD 4 + T细胞计数波动或接近稳定水平。特别地，如果应用阈值策略控制，则CD 4 + T细胞计数可以稳定在期望的水平。给药和停药的持续时间对规定的上限或下限阈值水平非常敏感，这可能解释了为什么具有固定时间表的开-停策略或具有频繁切换的STI策略与高失败率相关。我们的研究结果表明，这是至关重要的，要仔细选择阈值的CD 4 + T细胞计数和个性化的STI为每个患者的基础上初始CD 4 + T细胞计数。
The strategies of structured treatment interruptions (STIs) of antiretroviral therapies have been proposed for clinical management of HIV infected patients, but clinical studies on STIs failed to achieve a consistent conclusion for this strategy. To evaluate the STI strategies, in particular, CD4+ T cell count-guided STIs, and explain these controversial conclusions from different clinical studies, in this paper we propose to use piecewise HIV virus dynamic models to quantitatively explore the STI strategies and investigate their dynamic behaviors. Our analysis results indicate that CD4+ T cell counts can be maintained above a safe level using the STI with a single threshold or a threshold window. Numerical simulations show that the CD4+ T cell counts either fluctuate or approach a stable level for a patient, depending on the prescribed upper or lower threshold values. In particular, the CD4+ T cell counts can be stabilized at a desired level if the threshold policy control is applied. The durations of drug-on and drug-off are very sensitive to the prescribed upper or lower threshold levels, which possibly explains why the on-off strategy with fixed schedule or a STI strategy with frequent switches is associated with the high rate of failure. Our findings suggest that it is critical to carefully choose the thresholds of CD4+ T cell count and individualize the STIs for each individual patient based on initial CD4+ T cell counts.
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影响因子：
56.9
作者：
Blower, SM;Gershengorn, HB;Grant, RM
通讯作者：
Grant, RM
影响因子：
3.8
作者：
Ananworanich, J;Nuesch, R;Hirschel, B
通讯作者：
Hirschel, B
DOI：
10.1073/pnas.261568398
发表时间：
2001-12-18
影响因子：
11.1
作者：
Dybul, M;Chun, TW;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
3.5
作者：
Korobeinikov, A
通讯作者：
Korobeinikov, A
影响因子：
3.8
作者：
Maggiolo, Franco;Airoldi, Monica;Suter, Fredy
通讯作者：
Suter, Fredy