Viral blip dynamics during highly active antiretroviral therapy
Viral blip dynamics during highly active antiretroviral therapy
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DOI：
10.1128/jvi.77.22.12165-12172.2003
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发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
Perelson, AS
中科院分区：
文献类型：
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作者：
Di Mascio, M;Markowitz, M;Perelson, AS
尽管在抑制良好的高效抗逆转录病毒疗法(HAART)治疗的患者中经常观察到低水平病毒血症的间歇性发作，但病毒斑点的时间和幅度从未被详细研究过。我们在这里分析了123名接受HAART治疗的患者中病毒斑点的动态变化，即血浆VL测量为50拷贝/毫升，平均监测时间为2.6年(范围从5个月到5：3年)。平均(+/-标准差)斑点频率为0.09+/-0.11个样本，约三分之一的患者没有病毒斑点。病毒斑点的平均振幅为158+/-132人类免疫缺陷病毒1型(HIV-1)RNA拷贝/毫升。对斑点频率和振幅分布的分析表明，间隔小于22天的两个斑点很有可能是同一病毒血症的一部分。这些数据与假设模型一致，在该模型中，病毒血症的每一次发作都包括VL上升的一个阶段，然后是两个阶段的指数下降。因此，术语“病毒斑点”可能是一个用词不当，因为病毒复制似乎发生在一个较长的时期。病毒斑点的频率和幅度都不会随着观察时间的延长而增加，但在治疗开始时，病毒斑点的频率与CD4(+)-T细胞计数呈负相关，这表明宿主特有的因素而不是治疗疲劳是斑点频率的决定因素。
Although intermittent episodes of low-level viremia are often observed in well-suppressed highly active antiretroviral therapy (HAART)-treated patients, the timing and amplitude of viral blips have never been examined in detail. We analyze here the dynamics of viral blips, i.e., plasma VL measurements of >50 copies/ml, in 123 HAART-treated patients monitored for a mean of 2.6 years (range, 5 months to 5:3 years). The mean (+/- the standard deviation) blip frequency was 0.09 +/- 0.11/sample, with about one-third of patients showing no viral blips. The mean viral blip amplitude was 158 +/- 132 human immunodeficiency virus type 1 (HIV-1) RNA copies/ml. Analysis of the blip frequency and amplitude distributions suggest that two blips less than 22 days apart have a significant chance of being part of the same episode of viremia. The data are consistent with a hypothetical model in which each episode of viremia consists of a phase of VL rise, followed by two-phase exponential decay. Thus, the term "viral blip" may be a misnomer, since viral replication appears to be occurring over an extended period. Neither the frequency nor the amplitude of viral blips increases with longer periods of observation, but the frequency is inversely correlated with the CD4(+)-T-cell count at the start of therapy, suggesting that host-specific factors but not treatment fatigue are determinants of blip frequency.