Influence of delayed viral production on viral dynamics in HIV-1 infected patients
Influence of delayed viral production on viral dynamics in HIV-1 infected patients
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DOI：
10.1016/s0025-5564(98)10027-5
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发表时间：
1998-09-01
影响因子：
4.3
通讯作者：
Perelson, AS
中科院分区：
文献类型：
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作者：
Mittler, JE;Sulzer, B;Perelson, AS
我们提出并分析了人类免疫缺陷病毒1型（HIV-1）与靶细胞相互作用的模型，该模型包括初始感染和有效感染细胞形成之间的时间延迟。假设细胞之间的变化相对于这个“细胞内”的延迟可以近似的伽马分布，一个高度灵活的分布，可以模仿各种生物学上合理的延迟，我们提供了分析解决方案，预期的血浆病毒浓度下降后，开始抗逆转录病毒治疗与一种或多种蛋白酶抑制剂。然后，我们使用该模型来研究是否可以从生物数据中识别出表征病毒动力学的参数。使用非线性最小二乘回归拟合模型的模拟数据，其中的延迟符合伽马分布，我们表明，游离病毒清除率，感染细胞死亡率，和参数的伽马分布特征，可以得到很好的估计。对于使用其他生物学上合理的分布生成延迟的模拟数据集，可以使用伽马延迟模型获得病毒清除率、感染细胞死亡率和平均延迟时间的合理良好估计。对于包括添加的模拟噪声的模拟数据集，病毒清除率估计值并不可靠。如果细胞内的平均延迟是已知的，但是，我们表明，合理的估计病毒清除率可以通过采取谐波平均值的病毒清除率估计从一组患者。这些结果表明，有可能将分布的细胞内延迟纳入现有的HIV动力学模型，并使用这些改进的模型来估计游离病毒的半衰期，从HIV-1 RNA治疗后下降的数据。(C)1998年爱思唯尔科学公司All rights reserved.
We present and analyze a model for the interaction of human immunodeficiency virus type 1 (HIV-1) with target cells that includes a time delay between initial infection and the formation of productively infected cells. Assuming that the variation among cells with respect to this 'intracellular' delay can be approximated by a gamma distribution, a high flexible distribution that can mimic a variety of biologically plausible delays, we provide analytical solutions for the expected decline in plasma virus concentration after the initiation of antiretroviral therapy with one or more protease inhibitors. We then use the model to investigate whether the parameters that characterize viral dynamics can be identified from biological data. Using non-linear least-squares regression to fit the model to simulated data in which the delays conform to a gamma distribution, we show that good estimates for free viral clearance rates, infected cell death rates, and parameters characterizing the gamma distribution can be obtained. For simulated data sets in which the delays were generated using other biologically plausible distributions, reasonably good estimates for viral clearance rates, infected cell death rates, and mean delay times can be obtained using the gamma-delay model. For simulated data sets that include added simulated noise, viral clearance rate estimates are not as reliable. If the mean intracellular delay is known, however, we show that reasonable estimates for the viral clearance rate can be obtained by taking the harmonic mean of viral clearance rate estimates from a group of patients. These results demonstrate that it is possible to incorporate distributed intracellular delays into existing models for HIV dynamics and to use these refined models to estimate the half-life of free virus from data on the decline in HIV-1 RNA following treatment. (C) 1998 Elsevier Science Inc. All rights reserved.