Dixit Narendra M, Markowitz Martin, Ho David D, Perelson Alan S
Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
Antivir Ther. 2004 Apr;9(2):237-46.
We analyse viral load data of five patients under ritonavir monotherapy using a model of HIV dynamics under antiretroviral therapy that includes both drug pharmacokinetics and the intracellular delay from the time of cell infection to viral production. Using this approach we separate pharamacokinetic from intracellular delays, and obtain new estimates of intracellular delay and the antiviral efficacy of ritonavir. We find the average intracellular delay to be 1 day, in agreement with experiments. The average viral generation time is now estimated at 2 days, resulting in approximately 180 replication cycles per year. The model also reveals that ritonavir monotherapy is approximately 65% as efficacious as a recently used potent four-drug therapy, suggesting that selection for drug resistance may be facilitated by the relatively low efficacy of individual drugs, contributing in part to the inherent limitations of current therapies in combating HIV-1 infection.
我们使用一种抗逆转录病毒疗法下的HIV动力学模型，分析了接受利托那韦单一疗法的五名患者的病毒载量数据，该模型同时包含药物药代动力学以及从细胞感染到病毒产生的细胞内延迟。通过这种方法，我们将药代动力学延迟与细胞内延迟区分开来，并获得了细胞内延迟和利托那韦抗病毒疗效的新估计值。我们发现平均细胞内延迟为1天，这与实验结果一致。现在估计平均病毒生成时间为2天，每年约有180个复制周期。该模型还表明，利托那韦单一疗法的疗效约为最近使用的强效四联疗法的65%，这表明个体药物相对较低的疗效可能会促进耐药性的产生，这在一定程度上导致了当前疗法在对抗HIV-1感染方面的固有局限性。
