Role of HIV Reservoirs in the Pathogenesis of HIV Disease

在接受高活性抗逆转录病毒治疗（HAART）并成功抑制血浆病毒血症的人类免疫缺陷病毒（HIV）感染个体中，潜伏感染的、静止的携带复制能力HIV的CD4+ T细胞池的持久性已经得到了充分的证明。这种潜伏的病毒库被认为是在接受HAART治疗的感染者中完全根除艾滋病毒的主要障碍，因为它的半衰期很长，而且目前可用的药物在消除这些感染细胞方面无效；然而，这种病毒库的致病意义及其在HAART停药后血浆病毒血症反弹中的作用在很大程度上是未知的。我们之前已经证明，停止HAART治疗后血浆中病毒反弹的动力学与停止治疗前潜伏HIV病毒库的大小之间没有相关性，在这些感染者中，长期成功抑制了血浆病毒血症。利用异双工迁移率和跟踪试验，我们在本研究中证明，潜伏感染的可检测池，静止的CD4+ T细胞不能完全解释HAART已停止的感染者早期血浆HIV反弹。反弹的血浆病毒在遗传上不同于细胞相关的HIV RNA和在大多数被检测的潜伏感染的静止CD4+ T细胞中可检测到的复制能力病毒。这些结果表明，在停止HAART治疗后，存在其他持久性HIV病毒库，可能促使血浆病毒血症的迅速出现，并强调了开发针对这些受感染细胞群的治疗方法的必要性。

The persistence of a pool of latently infected, resting CD4+ T cells carrying replication-competent HIV has been well documented in human immunodeficiency virus (HIV)-infected individuals who are receiving highly active antiretroviral therapy (HAART) and in whom successful suppression of plasma viremia has been achieved. This latent viral reservoir is considered to be a major impediment to complete eradication of HIV in infected individuals receiving HAART due to its long half-life and the ineffectiveness of currently available drugs in eliminating these infected cells; however, the pathogenic significance of this viral reservoir as well as its role in the rebound of plasma viremia following discontinuation of HAART is largely unknown. We have previously demonstrated that there was no correlation between the kinetics of viral rebound in plasma upon cessation of HAART and the size of the latent HIV reservoir prior to discontinuation of therapy in infected individuals in whom prolonged periods of successful suppression of plasma viremia had been achieved. Using heteroduplex mobility and tracking assays, we demonstrate in this study that the detectable pool of latently infected, resting CD4+ T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued. The rebounding plasma virus was genetically distinct from both the cell-associated HIV RNA and replication-competent virus within the detectable pool of latently infected, resting CD4+ T cells in the majority of patients examined. These results suggest the existence of other persistent HIV reservoirs that could prompt rapid emergence of plasma viremia following cessation of HAART and underscore the necessity to develop therapies directed toward such populations of infected cells.