Hlavacek W S, Stilianakis N I, Perelson A S
Theoretical Division, Los Alamos National Laboratory, NM 87545, USA.
Philos Trans R Soc Lond B Biol Sci. 2000 Aug 29;355(1400):1051-8. doi: 10.1098/rstb.2000.0642.
In patients infected with human immunodeficiency virus type 1 (HIV-1), a large amount of virus is associated with follicular dendritic cells (FDCs) in lymphoid tissue. To assess the influence of FDCs on viral dynamics during antiretroviral therapy we have developed a mathematical model for treatment of HIV-1 infection that includes FDCs. Here, we use this model to analyse measurements of HIV-1 dynamics in the blood and lymphoid tissue of a representative patient, who was treated with a combination of HIV-1 reverse transcriptase and protease inhibitors. We show that loss of virus from FDCs during therapy can make a much larger contribution to plasma virus than production of virus by infected cells. This result challenges the notion that long-lived infected cells are a significant source of HIV-1 during drug therapy. Due to release of FDC-associated virus, we find that it is necessary to revise upward previous estimates of c, the rate at which free virus is cleared, and delta, the rate at which productively infected cells die. Furthermore, we find that potentially infectious virus, present before treatment, is released from FDCs during therapy and that the persistence of this virus can be affected by whether therapy includes reverse transcriptase inhibitors.
在感染了1型人类免疫缺陷病毒（HIV-1）的患者中，大量病毒与淋巴组织中的滤泡树突状细胞（FDC）相关。为了评估抗逆转录病毒治疗期间FDC对病毒动力学的影响，我们开发了一个用于治疗HIV-1感染的数学模型，该模型包含FDC。在此，我们使用这个模型来分析一名代表性患者血液和淋巴组织中HIV-1动力学的测量结果，该患者接受了HIV-1逆转录酶和蛋白酶抑制剂的联合治疗。我们表明，治疗期间FDC中病毒的损失对血浆病毒的贡献可能比被感染细胞产生的病毒大得多。这一结果挑战了长期存在的被感染细胞在药物治疗期间是HIV-1重要来源的观念。由于FDC相关病毒的释放，我们发现有必要向上修正先前对游离病毒清除率c和有生产能力的被感染细胞死亡率δ的估计。此外，我们发现治疗前存在的潜在感染性病毒在治疗期间从FDC中释放，并且这种病毒的持续存在可能会受到治疗是否包括逆转录酶抑制剂的影响。
