Jagarapu Aditya, Mann Rajveer, Piovoso Michael J, Zurakowski Ryan
Department of Biomedical Engineering, University of Delaware, USA.
Department of Biological Sciences, University of Delaware, USA.
Proc Am Control Conf. 2019 Jul;2019:3456-3461. doi: 10.23919/acc.2019.8815245. Epub 2019 Aug 29.
Combination Antiretroviral Therapy (cART) consists of a cocktail of drugs administered to HIV-infected patients that can suppress the amount of HIV in the patient's blood plasma to an undetectable level. Our previous work has suggested that some HIV-infected patients, despite being placed on cART, can still have ongoing viral replication occurring in self-sustaining inflamed lymph node follicle sanctuary sites. Spatial models of the putative sites show that inflammation is a necessary condition for ongoing HIV replication. In this study, we model the hypothesis that ongoing HIV replication may provide a sufficiently strong pro-inflammatory signal to maintain inflammation levels consistent with continued HIV replication. A system of ordinary differential equations integrated with a reactive-diffusion system is used to model the HIV dynamics and the diameter of a lymph node follicle as a function of time and external influence. The estimates of the parameters in our model come from prior data when available. The results of our study show that these dynamics have two stable steady-state solutions, one with low inflammation and no ongoing HIV replication in the site, and one with high inflammation and high levels of ongoing HIV replication in the site. We furthermore show that the system can transition between the two outcomes in response to a transient exogenous addition of pro-inflammatory signaling, consistent with the antigenic stimulus of a secondary infection. The spatial isolation of the sites results in a low viral load in the blood plasma for both conditions.
联合抗逆转录病毒疗法（cART）由多种药物混合而成，用于治疗HIV感染患者，可将患者血浆中的HIV数量抑制到检测不到的水平。我们之前的研究表明，一些HIV感染患者尽管接受了cART治疗，但在自我维持炎症的淋巴结滤泡庇护所部位仍可能存在持续的病毒复制。假定部位的空间模型显示，炎症是HIV持续复制的必要条件。在本研究中，我们建立了一个假设模型，即持续的HIV复制可能会提供足够强烈的促炎信号，以维持与HIV持续复制一致的炎症水平。使用一个常微分方程组与一个反应扩散系统相结合，来模拟HIV动态以及淋巴结滤泡直径随时间和外部影响的变化。我们模型中的参数估计值在有可用的先前数据时即取自这些数据。我们的研究结果表明，这些动态有两个稳定的稳态解，一个是炎症水平低且该部位无持续HIV复制，另一个是炎症水平高且该部位有高水平的持续HIV复制。我们还表明，该系统可以响应促炎信号的短暂外源添加而在两种结果之间转换，这与二次感染的抗原刺激一致。这些部位的空间隔离导致两种情况下血浆中的病毒载量都较低。
