University of North Carolina HIV Cure Center, UNC Chapel Hill School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Microbiology and Immunology, UNC Chapel Hill School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Viruses. 2023 Jul 31;15(8):1677. doi: 10.3390/v15081677.
Antiretroviral therapy (ART) has dramatically improved the prognosis for people living with HIV-1, but a cure remains elusive. The largest barrier to a cure is the presence of a long-lived latent reservoir that persists within a heterogenous mix of cell types and anatomical compartments. Efforts to eradicate the latent reservoir have primarily focused on latency reversal strategies. However, new work has demonstrated that the majority of the long-lived latent reservoir is established near the time of ART initiation, suggesting that it may be possible to pair an intervention with ART initiation to prevent the formation of a sizable fraction of the latent reservoir. Subsequent treatment with latency reversal agents, in combination with immune clearance agents, may then be a more tractable strategy for fully clearing the latent reservoir in people newly initiating ART. Here, we summarize molecular mechanisms of latency establishment and maintenance, ongoing efforts to develop effective latency reversal agents, and newer efforts to design latency prevention agents. An improved understanding of the molecular mechanisms involved in both the establishment and maintenance of latency will aid in the development of new latency prevention and reversal approaches to ultimately eradicate the latent reservoir.
抗逆转录病毒疗法 (ART) 极大地改善了 HIV-1 感染者的预后，但治愈仍然难以实现。治愈的最大障碍是存在一个长期存在的潜伏库，它存在于异质的细胞类型和解剖隔室混合体中。消除潜伏库的努力主要集中在潜伏逆转策略上。然而，新的研究表明，大多数长期潜伏库是在开始 ART 时建立的，这表明可能可以将干预措施与 ART 开始结合起来，以防止形成相当大比例的潜伏库。随后用潜伏逆转剂与免疫清除剂联合治疗，可能是一种更可行的策略，可用于在新开始接受 ART 的人群中完全清除潜伏库。在这里，我们总结了潜伏建立和维持的分子机制、正在开发有效潜伏逆转剂的努力，以及设计潜伏预防剂的新努力。对潜伏建立和维持涉及的分子机制的深入了解将有助于开发新的潜伏预防和逆转方法，最终消除潜伏库。
