Notermans D W, Goudsmit J, Danner S A, de Wolf F, Perelson A S, Mittler J
Department of Human Retrovirology, University of Amsterdam, The Netherlands.
AIDS. 1998 Aug 20;12(12):1483-90. doi: 10.1097/00002030-199812000-00010.
The dynamics uf viral decline following the initiation of antiretroviral treatment were studied in 29 HIV-1-infected patients participating in a two-arm trial comparing immediate (group A: ritonavir, zidovudine and lamivudine) and delayed (group B: ritonavir supplemented by zidovudine and lamivudine on day 21) triple therapy. Parameters underlying viral dynamics were estimated using mathematical models tailored to these treatment protocols.
The decline in plasma HIV-1 density between day 0 and 21 was steeper in group A (-2.27+/- 0.46 log10) than group B (-1.87+/-0.56 log10). In a subset of patients amenable to full mathematical analysis, a short-lived productively infected cell compartment (producing approximately 97% of total virions) decayed with a half-life of 1.0-2.5 days, whereas a long-lived infected cell compartment decayed with a half-life of 18.8-32.8 days. Estimates for the time for the elimination of virus from these two cell populations ranged from 474 to 802 days. The rate of loss of productively infected CD4+ T cells was positively correlated with baseline viral load in group A and in the combined dataset.
These results suggest that HIV-infected cell populations may have a faster turnover in patients with higher viral loads due to higher infection rate parameters, higher rates of virus production, or lower virus clearance rates.
在一项双臂试验中,对29例HIV-1感染患者启动抗逆转录病毒治疗后的病毒下降动力学进行了研究。该试验比较了立即(A组:利托那韦、齐多夫定和拉米夫定)和延迟(B组:第21天开始用齐多夫定和拉米夫定补充利托那韦)三联疗法。使用针对这些治疗方案定制的数学模型估计病毒动力学的相关参数。
第0天至21天期间,A组血浆HIV-1密度下降幅度(-2.27±0.46 log10)比B组(-1.87±0.56 log10)更陡峭。在一组适合进行完整数学分析的患者中,一个短暂存在的高效感染细胞区室(产生约97%的总病毒体)以1.0 - 2.5天的半衰期衰减,而一个长寿感染细胞区室以18.8 - 32.8天的半衰期衰减。从这两个细胞群体中清除病毒的时间估计为474至802天。A组以及合并数据集中,高效感染的CD4 + T细胞损失率与基线病毒载量呈正相关。
这些结果表明,由于感染率参数较高、病毒产生率较高或病毒清除率较低,HIV感染细胞群体在病毒载量较高的患者中可能具有更快的更新率。