Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bioessays. 2013 Jun;35(6):544-52. doi: 10.1002/bies.201200170. Epub 2013 Apr 24.
The discovery of a stable latent reservoir for HIV-1 in resting memory CD4(+) T cells provides a mechanism for lifelong persistence of HIV-1. The long-lived latently infected cells persist in spite of prolonged highly active antiretroviral therapy and present a major barrier to a cure of HIV-1 infection. In this review, we discuss the current understanding of HIV-1 persistence and latent viral infection in the context of effective antiretroviral therapy and the recent progress in purging latent viral reservoirs. Recent studies demonstrate that reactivation of latent HIV-1 is a promising strategy for the depletion of these viral reservoirs. A thorough evaluation of the anti-latency activity of drug candidates should include the measurement of changes in intracellular viral RNA, plasma virus levels, and the size of latent viral reservoirs, as well as potential adverse effects. Currently, there are several technical barriers to the evaluation of anti-latency drugs in vivo. We also discuss these challenging issues that remain unresolved.
HIV-1 潜伏储库在静止记忆性 CD4(+)T 细胞中的稳定发现为 HIV-1 的终身持续存在提供了一种机制。尽管进行了长期的高效抗逆转录病毒治疗，但这些长期潜伏感染的细胞仍持续存在，这是治愈 HIV-1 感染的主要障碍。在这篇综述中，我们讨论了在有效抗逆转录病毒治疗背景下 HIV-1 持续存在和潜伏性病毒感染的最新进展，以及清除潜伏性病毒储库的最新进展。最近的研究表明，潜伏 HIV-1 的激活是消耗这些病毒储库的有前途的策略。对候选药物的抗潜伏活性的彻底评估应包括测量细胞内病毒 RNA、血浆病毒水平和潜伏病毒储库的大小以及潜在的不良反应。目前，在体内评估抗潜伏药物存在几个技术障碍。我们还讨论了这些尚未解决的具有挑战性的问题。
