Di Mascio Michele, Ribeiro Ruy M, Markowitz Martin, Ho David D, Perelson Alan S
Theoretical Division, Los Alamos National Laboratory, 1 Los Alamos Lab, Los Alamos, NM 87545-0001, USA.
Math Biosci. 2004 Mar-Apr;188:47-62. doi: 10.1016/j.mbs.2003.08.003.
Highly active antiretroviral therapy (HAART), administered to a HAART-naïve patient, perturbs the steady state of chronic infection. This perturbation provides an opportunity to investigate the existence and dynamics of different sources of viral production. Models of HIV dynamics can be used to make a comparative analysis of the efficacies of different drug regimens. When HAART is administered for long periods of time, most patients achieve 'undetectable' viral loads (VLs), i.e., below 50 copies/ml. Use of an ultrasensitive VL assay demonstrates that some of these patients obtain a low steady state VL in the range 5-50 copies/ml, while others continue to exhibit VL declines to below 5 copies/ml. Interestingly, when patients exhibit continued declines below 50 copies/ml the virus has a half-life of approximately 6 months, consistent with some estimates of the rate of latent cell decline. Some patients, despite having sustained undetectable VLs, show periods of transient viremia (blips). We present a statistical characterization of the blips observed in a set of 123 patients, suggesting that patients have different tendencies to show blips during the period of VL suppression, that intermittent episodes of viremia have common amplitude profiles, and that VL decay from the peak of a blip may have two phases.
给予从未接受过高效抗逆转录病毒治疗(HAART)的患者高效抗逆转录病毒治疗,会扰乱慢性感染的稳态。这种扰动为研究病毒产生的不同来源的存在和动态提供了机会。HIV动力学模型可用于对不同药物治疗方案的疗效进行比较分析。长期进行HAART治疗时,大多数患者可实现病毒载量(VL)“检测不到”,即低于50拷贝/毫升。使用超灵敏VL检测方法表明,其中一些患者的VL在5 - 50拷贝/毫升范围内达到低稳态,而另一些患者的VL则持续下降至低于5拷贝/毫升。有趣的是,当患者的VL持续下降至低于50拷贝/毫升时,病毒的半衰期约为6个月,这与一些潜伏细胞下降速率的估计一致。一些患者尽管VL持续检测不到,但仍会出现短暂病毒血症期(波动)。我们对一组123例患者中观察到的波动进行了统计特征分析,结果表明患者在VL抑制期出现波动的倾向不同,病毒血症的间歇性发作具有共同的幅度特征,并且从波动峰值开始的VL衰减可能有两个阶段。