Sánchez-Taltavull Daniel, Alarcón Tomás
Centre de Recerca Matemàtica, Edifici C, Campus de Bellaterra, 08193 Bellaterra (Barcelona), Spain; Departament de Matemàtica Aplicada i Anàlisi, Universitat de Barcelona, 08007 Barcelona, Spain.
Centre de Recerca Matemàtica, Edifici C, Campus de Bellaterra, 08193 Bellaterra (Barcelona), Spain; Departament de Matemàtiques, Universitat Atonòma de Barcelona, 08193 Bellaterra (Barcelona), Spain.
J Theor Biol. 2015 Apr 21;371:79-89. doi: 10.1016/j.jtbi.2015.02.001. Epub 2015 Feb 11.
We propose a stochastic model of HIV-1 infection dynamics under HAART in order to analyse the origin and dynamics of the so-called viral blips, i.e. episodes of transient viremia that occur in the phase of where the disease remains in a latent state during which the viral load raises above the detection limit of standard clinical assays. Based on prior work in the subject, we consider an infection model in which latently infected cell compartment sustains a residual (latent) infection over long periods of time. Unlike previous models, we include the effects of inhomogeneities in cell and virus concentration in the blood stream. We further consider the effect of burst virion production. By comparing with the experimental results obtained during a study in which intensive sampling was carried out on HIV-1-infected patients undergoing HAART over a long period of time, we conclude that our model supports the hypothesis that viral blips are consistent with random fluctuations around the average viral load. We further observe that agreement between our simulation results and the blip statistics obtained in the aforementioned study improves when burst virion production is considered. We also study the effect of sample manipulation artifacts on the results produced by our model, in particular, that of the post-extraction handling time, i.e. the time elapsed between sample extraction and actual test. Our results support the notion that the statistics of viral blips can be critically affected by such artifacts.
我们提出了一种在高效抗逆转录病毒治疗(HAART)下的HIV-1感染动态随机模型,以分析所谓病毒波动的起源和动态,即疾病处于潜伏状态期间病毒载量升高超过标准临床检测方法检测限的短暂病毒血症发作。基于该领域先前的工作,我们考虑一种感染模型,其中潜伏感染细胞隔室在很长一段时间内维持残余(潜伏)感染。与先前的模型不同,我们纳入了血流中细胞和病毒浓度不均匀性的影响。我们还考虑了病毒粒子爆发产生的影响。通过与在一项对接受HAART的HIV-1感染患者进行长期密集采样的研究中获得的实验结果进行比较,我们得出结论,我们的模型支持病毒波动与平均病毒载量周围的随机波动一致的假设。我们还观察到,当考虑病毒粒子爆发产生时,我们的模拟结果与上述研究中获得的波动统计数据之间的一致性得到改善。我们还研究了样本处理假象对我们模型产生的结果的影响,特别是提取后处理时间的影响,即样本提取与实际检测之间经过的时间。我们的结果支持这样一种观点,即病毒波动的统计数据可能会受到此类假象的严重影响。