Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20128 Milan, Italy.
Cells. 2021 Dec 28;11(1):77. doi: 10.3390/cells11010077.
Since its discovery 35 years ago, there have been no therapeutic interventions shown to enable full HIV-1 remission. Combined antiretroviral therapy (cART) has achieved the sustained control of HIV-1 replication, however, the life-long treatment does not eradicate long-lived latently infected reservoirs and can result in multiple side effects including the development of multidrug-resistant escape mutants. Antibody-based treatments have emerged as alternative approaches for a HIV-1 cure. Here, we will review clinical advances in coreceptor-targeting antibodies, with respect to anti-CCR5 antibodies in particular, which are currently being generated to target the early stages of infection. Among the Env-specific antibodies widely accepted as relevant in cure strategies, the potential role of those targeting CD4-induced (CD4i) epitopes of the CD4-binding site (CD4bs) in eliminating HIV-1 infected cells has gained increasing interest and will be presented. Together, with approaches targeting the HIV-1 replication cycle, we will discuss the strategies aimed at boosting and modulating specific HIV-1 immune responses, highlighting the harnessing of TLR agonists for their dual role as latency reverting agents (LRAs) and immune-modulatory compounds. The synergistic combinations of different approaches have shown promising results to ultimately enable a HIV-1 cure.
自 35 年前发现以来，尚无能够实现 HIV-1 完全缓解的治疗干预措施。联合抗逆转录病毒疗法（cART）已实现了对 HIV-1 复制的持续控制，然而，终身治疗并不能消除长期潜伏感染的储库，并且可能导致多种副作用，包括多药耐药逃逸突变体的产生。基于抗体的治疗方法已成为 HIV-1 治愈的替代方法。在这里，我们将回顾针对辅助受体的抗体的临床进展，特别是针对抗 CCR5 抗体的进展，目前正在开发这些抗体以针对感染的早期阶段。在被广泛认为与治愈策略相关的Env 特异性抗体中，针对 CD4 结合位点（CD4bs）上的 CD4 诱导（CD4i）表位的抗体在消除 HIV-1 感染细胞方面的潜在作用引起了越来越多的关注，并将进行介绍。与针对 HIV-1 复制周期的方法一起，我们将讨论旨在增强和调节特定 HIV-1 免疫反应的策略，强调利用 TLR 激动剂作为潜伏逆转剂（LRA）和免疫调节化合物的双重作用。不同方法的协同组合已显示出有希望的结果，最终实现 HIV-1 的治愈。
