Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7, QC, Canada.
Centre de Recherche de l'Université de Montréal, Montréal, QC, Canada.
Cytokine Growth Factor Rev. 2018 Apr;40:90-98. doi: 10.1016/j.cytogfr.2018.03.010. Epub 2018 Apr 5.
Antiretroviral therapy (ART) has dramatically reduced HIV-1-associated morbidity and mortality, and has transformed HIV-1 infection into a manageable chronic condition by suppressing viral replication. However, despite recent patient care improvements, ART still fails to cure HIV-1 infection due to the inability to counteract immune defects and metabolic disturbances that are associated with residual inflammation alongside viral persistence. Life-long drug administration also results in multiple side-effects in patients including lipodystrophy and insulin resistance. Thus, it is critical to find new ways to reduce the length of treatment and facilitate the termination of ART, for example by boosting protective immunity. The rare ability of some individuals to naturally control HIV-1 infection despite residual inflammation could be exploited to identify molecular mechanisms involved in host protection that may function as potential therapeutic targets. In this review, we highlight evidence illustrating the molecular and metabolic advantages of HIV-1 controllers over ART treated patients that contribute to the maintenance of effective antiviral immunity.
抗逆转录病毒疗法（ART）显著降低了 HIV-1 相关发病率和死亡率，并通过抑制病毒复制将 HIV-1 感染转化为可管理的慢性疾病。然而，尽管最近改善了患者护理，但由于无法克服与残留炎症以及病毒持续存在相关的免疫缺陷和代谢紊乱，ART 仍然无法治愈 HIV-1 感染。终身药物治疗还会导致患者出现多种副作用，包括脂肪营养不良和胰岛素抵抗。因此，寻找新的方法来缩短治疗时间并促进 ART 的终止至关重要，例如通过增强保护性免疫。尽管存在炎症，但一些人能够自然控制 HIV-1 感染的罕见能力可以被利用来识别参与宿主保护的分子机制，这些机制可能作为潜在的治疗靶点。在这篇综述中，我们强调了 HIV-1 控制器相对于接受 ART 治疗的患者在分子和代谢方面的优势的证据，这些优势有助于维持有效的抗病毒免疫。
