Di Mascio Michele, Markowitz Martin, Louie Michael, Hurley Arlene, Hogan Christine, Simon Viviana, Follmann Dean, Ho David D, Perelson Alan S
Theoretical Division, Los Alamos National Laboratory, New Mexico, USA.
J Virol. 2004 Oct;78(19):10566-73. doi: 10.1128/JVI.78.19.10566-10573.2004.
The meaning of viral blips in human immunodeficiency virus type 1 (HIV-1)-infected patients treated with seemingly effective highly active antiretroviral therapy (HAART) is still controversial and under investigation. Blips might represent low-level ongoing viral replication in the presence of drug or simply release of virions from the latent reservoir. Patients treated early during HIV-1 infection are more likely to have a lower total body viral burden, a homogenous viral population, and preserved HIV-1-specific immune responses. Consequently, viral blips may be less frequent in them than in patients treated during chronic infection. To test this hypothesis, we compared the occurrence of viral blips in 76 acutely infected patients (primary HIV infection [PHI] group) who started therapy within 6 months of the onset of symptoms with that in 47 patients who started HAART therapy during chronic infection (chronic HIV infection [CHI] group). Viral blip frequency was approximately twofold higher in CHI patients (0.122 +/- 0.12/viral load [VL] sample, mean +/- standard deviation) than in PHI patients (0.066 +/- 0.09/VL sample). However, in both groups, viral blip frequency did not increase with longer periods of observation. Also, no difference in viral blip frequency was observed between treatment subgroups, and the occurrence of a blip was not associated with a recent change in CD4(+) T-cell count. Finally, in PHI patients the VL set point was a significant predictor of blip frequency during treatment.
在接受看似有效的高效抗逆转录病毒疗法(HAART)治疗的1型人类免疫缺陷病毒(HIV-1)感染患者中,病毒波动的意义仍存在争议且正在研究中。病毒波动可能代表在有药物存在的情况下低水平的持续病毒复制,或者仅仅是病毒粒子从潜伏库中的释放。在HIV-1感染早期接受治疗的患者更有可能具有较低的全身病毒载量、均匀的病毒群体以及保留的HIV-1特异性免疫反应。因此,与慢性感染期间接受治疗的患者相比,他们出现病毒波动的频率可能更低。为了验证这一假设,我们比较了76名急性感染患者(原发性HIV感染[PHI]组)在症状出现后6个月内开始治疗时与47名慢性感染期间开始HAART治疗的患者(慢性HIV感染[CHI]组)中病毒波动的发生情况。CHI组患者的病毒波动频率(0.122±0.12/病毒载量[VL]样本,平均值±标准差)比PHI组患者(0.066±0.09/VL样本)高出约两倍。然而,在两组中,病毒波动频率并未随着观察时间的延长而增加。此外,在治疗亚组之间未观察到病毒波动频率的差异,并且病毒波动的发生与CD4(+) T细胞计数的近期变化无关。最后,在PHI患者中,VL设定点是治疗期间病毒波动频率的一个重要预测指标。