HIV-1 entry inhibitors: recent development and clinical use.
HIV-1 entry inhibitors: recent development and clinical use.
复制标题
HIV-1进入抑制剂：最近的开发和临床用途。
DOI：
10.1016/j.coviro.2012.12.002
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发表时间：
2013-02
影响因子：
5.9
通讯作者：
Kuritzkes, Daniel R.
中科院分区：
文献类型：
--
作者：
Henrich, Timothy J.;Kuritzkes, Daniel R.
这篇综述提供了HIV-1进入抑制剂的概述，重点是临床开发后期的药物。HIV-1进入靶细胞涉及病毒附着、共受体结合和融合。抗逆转录病毒药物可以与进入过程中的每个步骤相互作用，但目前只有两种药物被批准用于临床。小分子附着抑制剂BMS-663068在早期研究中显示出有效的抗病毒活性，目前正在进行2b期试验。附着后抑制剂ibalizumab在1期和2期试验中显示出抗病毒活性；进一步的研究，包括对健康个体的皮下给药，是值得期待的。CCR5拮抗剂maraviroc被批准用于treatment-naïve和有治疗经验的患者。Cenicriviroc是一种小分子CCR5拮抗剂，也具有CCR2拮抗剂的活性，已进入2b期研究。目前还没有CXCR4拮抗剂进入临床试验，但每天都有新一代可注射肽融合抑制剂进入人体试验。目前正在研究maraviroc和ibalizumab用于预防HIV-1传播和/或用于核苷类逆转录酶抑制剂的抗逆转录病毒治疗方案。抑制HIV-1进入仍然是抗逆转录病毒药物开发的一个有希望的目标。
This review provides an overview of HIV-1 entry inhibitors, with a focus on drugs in the later stages of clinical development. Entry of HIV-1 into target cells involves viral attachment, co-receptor binding and fusion. Antiretroviral drugs that interact with each step in the entry process have been developed, but only two are currently approved for clinical use. The small molecule attachment inhibitor BMS-663068 has shown potent antiviral activity in early phase studies, and phase 2b trials are currently underway. The post-attachment inhibitor ibalizumab has shown antiviral activity in phase 1 and 2 trials; further studies, including subcutaneous delivery of drug to healthy individuals, are anticipated. The CCR5 antagonist maraviroc is approved for use in treatment-naïve and treatment-experienced patients. Cenicriviroc, a small-molecule CCR5 antagonist that also has activity as a CCR2 antagonist, has entered phase 2b studies. No CXCR4 antagonists are currently in clinical trials, but once daily, next-generation injectable peptide fusion inhibitors have entered human trials. Both maraviroc and ibalizumab are being studied for prevention of HIV-1 transmission and/or for use in nucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens. Inhibition of HIV-1 entry continues to be a promising target for antiretroviral drug development.
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