The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
J Theor Biol. 2009 Aug 21;259(4):751-9. doi: 10.1016/j.jtbi.2009.04.010. Epub 2009 Apr 21.
Primary human immunodeficiency virus (HIV) infection is characterized by an initial exponential increase of viral load in peripheral blood reaching a peak, followed by a rapid decline to the viral setpoint. Although the target-cell-limited model can account for part of the viral kinetics observed early in infection [Phillips, 1996. Reduction of HIV concentration during acute infection: independence from a specific immune response. Science 271 (5248), 497-499], it frequently predicts highly oscillatory kinetics after peak viremia, which is not typically observed in clinical data. Furthermore, the target-cell-limited model is unable to predict long-term viral kinetics, unless a delayed immune effect is assumed [Stafford et al., 2000. Modeling plasma virus concentration during primary HIV infection. J. Theor. Biol. 203 (3), 285-301]. We show here that extending the target-cell-limited model, by implementing a saturation term for HIV-infected cell loss dependent upon infected cell levels, is able to reproduce the diverse observed viral kinetic patterns without the assumption of a delayed immune response. Our results suggest that the immune response may have significant effect on the control of the virus during primary infection and may support experimental observations that an anti-HIV immune response is already functional during peak viremia.
原发性人类免疫缺陷病毒（HIV）感染的特征是外周血中病毒载量的初始指数增长，达到峰值，然后迅速下降到病毒基准。尽管靶细胞限制模型可以解释感染早期观察到的部分病毒动力学[Phillips，1996.急性感染期间 HIV 浓度的降低：与特定免疫反应无关。科学 271（5248），497-499]，但它经常预测在峰值病毒血症后出现高度振荡动力学，这在临床数据中并不常见。此外，除非假设延迟的免疫效应，否则靶细胞限制模型无法预测长期病毒动力学[Stafford 等人，2000.原发性 HIV 感染期间血浆病毒浓度建模。J.理论生物学 203（3），285-301]。我们在这里表明，通过实施依赖于感染细胞水平的 HIV 感染细胞丧失的饱和项来扩展靶细胞限制模型，能够在不假设延迟免疫反应的情况下再现多样化的观察到的病毒动力学模式。我们的结果表明，免疫反应可能对原发性感染期间病毒的控制有重大影响，并支持实验观察，即在峰值病毒血症期间已经存在抗 HIV 免疫反应。
