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通过使用强效抗病毒药物,能否根除 HIV 感染?

Can HIV infection be eradicated through use of potent antiviral agents?

机构信息

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Sweden.

出版信息

Curr Opin Infect Dis. 2010 Dec;23(6):628-32. doi: 10.1097/QCO.0b013e32833ff1d0.

Abstract

PURPOSE OF REVIEW

This review focuses on recent advances in HIV research and therapy that seek to eradicate persistent HIV in patients on suppressive therapy.

RECENT FINDINGS

The source of persistent HIV in patients on suppressive therapy is debated. Recent studies of treatment intensification have produced varied results: no reduction in low-level plasma viremia indicating the source of persistent viremia is long-lived HIV-infected cells that release HIV when activated and increase in episomal HIV DNA indicating active replication persists in some infected individuals on suppressive therapy. In addition, clonal HIV sequences found in plasma from patients on long-term suppressive therapy are rarely found in CD4+ memory T cells. These results indicate that persistent viremia may arise from several different sources. Recent studies emphasize the complexity of HIV latency. Current strategies for HIV eradication focus on compounds that activate viral transcription in memory CD4+ T cells by many routes, including inhibiting histone deacetylation and activating nuclear factor kappa B. Several compounds and combinations of these compounds appear to induce the expression of integrated HIV in different latency models.

SUMMARY

The eradication of HIV requires the elimination of persistent HIV during suppressive therapy. Recent studies have focused on the source of persistent viremia, mechanisms of intracellular HIV latency, and reactivation of latent HIV. It remains to be seen whether alternative treatment strategies may be required to eradicate HIV.

摘要

目的综述

本篇综述聚焦于 HIV 研究和治疗方面的最新进展,旨在消除接受抑制性治疗患者体内的持续性 HIV。

最近发现

接受抑制性治疗的患者体内持续性 HIV 的来源存在争议。最近关于强化治疗的研究结果各异:并未降低低水平血浆病毒载量,这表明持续性病毒血症的来源是寿命较长的 HIV 感染细胞,这些细胞在被激活时会释放 HIV,而游离 HIV DNA 的增加则表明在接受抑制性治疗的一些感染者中,活跃的复制仍在持续。此外,在接受长期抑制性治疗的患者的血浆中发现的克隆性 HIV 序列很少在 CD4+记忆 T 细胞中发现。这些结果表明持续性病毒血症可能有多种不同的来源。最近的研究强调了 HIV 潜伏期的复杂性。目前消除 HIV 的策略集中在通过多种途径激活记忆 CD4+T 细胞中病毒转录的化合物上,包括抑制组蛋白去乙酰化和激活核因子 kappa B。几种化合物及其组合似乎在不同的潜伏期模型中诱导整合 HIV 的表达。

总结

要消除 HIV,就需要在抑制性治疗期间消除持续性 HIV。最近的研究集中在持续性病毒血症的来源、细胞内 HIV 潜伏期的机制以及潜伏 HIV 的激活上。是否需要替代治疗策略来消除 HIV 还有待观察。

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