Role Of Viral Reservoirs In The Pathogenesis Of HIV Dise

有效的抗病毒治疗的使用导致了艾滋病毒复制的快速和持续的抑制，并极大地改善了绝大多数接受最佳治疗的感染者的临床结果。然而，主要由于各种病毒库的持续存在，在接受有效抗病毒治疗的感染者中无法根除艾滋病毒。其中，静息的CD4+T细胞隔间中的潜伏感染细胞池是研究最广泛的细胞之一，被认为是根除艾滋病毒的主要障碍。这种潜伏的艾滋病毒宿主的固有半衰期极长，可能使接受目前可用的抗病毒治疗的患者几乎不可能根除病毒。然而，过去几年进行的研究表明，持续的低水平病毒复制持续存在，因此延长了接受抗病毒治疗的患者的艾滋病毒总体半衰期。在过去的一年里，我们调查了一组患者中残留艾滋病毒的存在和状况，这些患者接受了不间断的抗病毒治疗，使他们持续无菌。在所有研究对象中，我们都证明了具有复制能力的病毒在CD4+T细胞中持续存在。令人惊讶的是，在所研究的大多数患者中，与静止的CD4+T细胞相比，激活的CD4+T细胞中的HIV前病毒DNA水平显著更高。此外，我们证明，尽管多年有效的抗病毒治疗，肠道中相对较高频率的CD4+T细胞携带艾滋病毒前病毒DNA。系统发育分析显示，外周血腔内静息和激活的CD4+T细胞与肠道末端回肠和乙状结肠中的CD4+T细胞之间存在交叉感染，这表明这些患者可能发生了潜伏感染的静息CD4+T细胞的持续重新激活和肠道内激活的CD4+T细胞传播病毒的情况。这样的事件可能允许持续补充CD4+T细胞储存库，并重新设定潜伏感染的静止CD4+T细胞的半衰期，尽管存在长时间的无血症。

The use of effective antiviral therapy has led to rapid and sustained suppression of HIV replication and has dramatically improved the clinical outcome in the vast majority of infected individuals who are treated optimally. However, it has not been possible to eradicate HIV in infected individuals receiving effective antiviral therapy mainly due to the persistence of various viral reservoirs. Among those, a pool of latently infected cells in the resting CD4+ T cell compartment has been one of the most extensively studied and is considered to be a major impediment to HIV eradication. The extremely long intrinsic half-life of such a latent HIV reservoir may make eradication of the virus all but impossible in patients receiving currently available antiviral therapy. However, studies conducted over the past several years suggest that low levels of ongoing viral replication persist and consequently prolong the overall half-life of HIV in patients receiving antiviral therapy. In the past year, we investigated the presence and status of residual HIV in a cohort of patients who had received uninterrupted antiviral therapy that rendered them consistently aviremic. We demonstrated the persistence of replication-competent virus in CD4+ T cells in all study subjects. Surprisingly, substantially higher levels of HIV proviral DNA were found in activated CD4+ T cells when compared to resting CD4+ T cells in the majority of patients studied. In addition, we demonstrated that relatively high frequencies of CD4+ T cells in the gut carried HIV proviral DNA despite years of effective antiviral therapy. Phylogenetic analyses showed evidence for cross-infection among resting and activated CD4+ T cells in the peripheral blood compartment and CD4+ T cells in terminal ileum and sigmoid colon in the gut, suggesting that on-going reactivation of latently infected, resting CD4+ T cells and spread of virus by activated CD4+ T cells in the gut may occur in these patients. Such events may allow continual replenishment of the CD4+ T cell reservoir and resetting of the half-life of the latently infected, resting CD4+ T cells despite prolonged periods of aviremia.