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以巨噬细胞为重点的不同细胞储存库中抗逆转录病毒药物的潜在机制。

Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages.

作者信息

Aquaro Stefano, Borrajo Ana, Pellegrino Michele, Svicher Valentina

机构信息

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.

Department of Experimental Medicine, University of Rome Tor Vergata, Roma, Italy.

出版信息

Virulence. 2020 Dec;11(1):400-413. doi: 10.1080/21505594.2020.1760443.

Abstract

Ongoing with current combinations of antiretroviral drugs for the treatment of Human Immunodeficiency Virus (HIV) infection can successfully maintain long-term suppression of HIV-1 replication in plasma. Still, none of these therapies is capable of extinguishing the virus from the long-lived cellular reservoir, including monocyte-derived macrophages (MDM), that means the principal obstacle to HIV cure. MDM are widely distributed in all tissues and organs, including central system nervous (CNS) where they represent the most frequent HIV-infected cells that means the principal obstacle to HIV cure. Current FDA-approved antiretroviral drugs target viral reverse transcriptase, protease, integrase, and entry processes (coreceptor or fusion blockade). It is desirable to continue to develop new antiretrovirals directed against alternative targets in the virus lifecycle in order to further optimize therapeutic options, overcome resistance to existing medications, and potentially contribute to the elimination of viral reservoirs.This review provides a comprehensive overview of the activity of antiretroviral drugs (classical and upcoming) in monocytes-derived macrophages (MDM). Defining the antiviral activity of these drugs in this important cellular HIV-1 reservoir provides crucial hints about their efficacy in HIV-1 infected patients.

摘要

继续使用目前的抗逆转录病毒药物组合治疗人类免疫缺陷病毒(HIV)感染能够成功维持对血浆中HIV-1复制的长期抑制。然而,这些疗法均无法从包括单核细胞衍生的巨噬细胞(MDM)在内的长寿细胞储存库中清除病毒,这意味着HIV治愈的主要障碍。MDM广泛分布于所有组织和器官,包括中枢神经系统(CNS),在那里它们是最常见的HIV感染细胞,这意味着HIV治愈的主要障碍。目前美国食品药品监督管理局(FDA)批准的抗逆转录病毒药物靶向病毒逆转录酶、蛋白酶、整合酶和进入过程(共受体或融合阻断)。继续开发针对病毒生命周期中其他靶点的新型抗逆转录病毒药物,以进一步优化治疗方案、克服对现有药物的耐药性,并有可能有助于消除病毒储存库,这是很有必要的。本综述全面概述了抗逆转录病毒药物(经典药物和即将上市的药物)在单核细胞衍生的巨噬细胞(MDM)中的活性。确定这些药物在这个重要的HIV-1细胞储存库中的抗病毒活性,为它们在HIV-1感染患者中的疗效提供了关键线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/7219522/1c71cf40a50d/kvir-11-01-1760443-g001.jpg

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