Sedaghat Ahmad R, Siliciano Robert F, Wilke Claus O
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore Maryland 21205, USA.
BMC Infect Dis. 2008 Jan 2;8:2. doi: 10.1186/1471-2334-8-2.
In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells.
Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART.
By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model.
The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.
在高效抗逆转录病毒疗法（HAART）的背景下，人类免疫缺陷病毒1型（HIV-1）的血浆水平迅速下降至标准临床检测方法的检测限以下。然而，残留的潜伏感染记忆CD4 + T细胞的重新激活是持续产生病毒的一个来源，这迫使患者尽管病毒载量在临床上无法检测到仍需继续接受HAART治疗。不幸的是，潜伏库衰减缓慢，半衰期长达44个月，这使其成为根除HIV-1感染的主要已知障碍。然而，潜伏库长半衰期的潜在机制尚不清楚。最可能的潜在机制是低水平病毒复制和潜伏感染细胞的内在稳定性。
在此，我们使用HIV-1感染背景下T细胞动力学的数学模型来探究HAART启动后潜伏库的衰减特征。我们将该模型的行为与患者来源的数据进行比较，以深入了解低水平病毒复制在HAART背景下的作用。
通过将我们模型的行为与患者来源的数据进行比较，我们发现接受HAART治疗的患者中观察到的病毒动力学可能与低水平病毒复制一致，但这种复制不会显著影响潜伏库的衰减率。根据我们模型的预测，潜伏感染细胞的内在稳定性及其重新激活的速率而非低水平复制，主要决定了观察到的潜伏库衰减率。
潜伏库的内在稳定性对根除HIV-1感染的努力具有重要意义，并表明强化HAART不会加速潜伏库的衰减。
