Clinical use of CCR5 inhibitors in HIV and beyond.
Clinical use of CCR5 inhibitors in HIV and beyond.
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DOI：
10.1186/1479-5876-9-s1-s9
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发表时间：
2011-01-27
影响因子：
7.4
通讯作者：
Redfield RR
中科院分区：
文献类型：
--
作者：
Gilliam BL;Riedel DJ;Redfield RR
自从发现CCR5作为HIV进入的辅助受体以来，人们一直对阻断该受体以治疗和预防HIV感染感兴趣。尽管几种CCR5拮抗剂已在临床试验中进行了评估，但只有马拉韦罗已被批准用于治疗HIV感染患者的临床用途。本文沿着综述了以马拉韦罗为重点的CCR5拮抗剂的疗效、安全性和耐药性，以及它们在特殊和新兴临床情况下的应用。尽管自2007年以来已被批准使用，但马拉韦罗在艾滋病毒和其他疾病中的最佳使用尚未明确。Maraviroc和其他CCR5拮抗剂具有用于各种其他临床情况的潜力，例如预防HIV传播，加强HIV治疗和预防器官移植中的排斥反应。CCR5拮抗剂的使用可通过下调CCR5受体从而降低CCR5密度的其它试剂如雷帕霉素来增强。它们甚至可能与其他进入抑制剂联合使用。然而，CCR5拮抗剂的临床使用可能在疾病如西尼罗河和蜱传脑炎病毒感染中具有负面后果。总之，CCR5拮抗剂在治疗和预防HIV以及未来在器官移植等新情况下的应用中具有巨大的治疗潜力。它们单独使用或与其他药物联合使用的最佳用途将通过进一步研究确定。
Since the discovery of CCR5 as a coreceptor for HIV entry, there has been interest in blockade of the receptor for treatment and prevention of HIV infection. Although several CCR5 antagonists have been evaluated in clinical trials, only maraviroc has been approved for clinical use in the treatment of HIV-infected patients. The efficacy, safety and resistance profile of CCR5 antagonists with a focus on maraviroc are reviewed here along with their usage in special and emerging clinical situations. Despite being approved for use since 2007, the optimal use of maraviroc has yet to be well-defined in HIV and potentially in other diseases. Maraviroc and other CCR5 antagonists have the potential for use in a variety of other clinical situations such as the prevention of HIV transmission, intensification of HIV treatment and prevention of rejection in organ transplantation. The use of CCR5 antagonists may be potentiated by other agents such as rapamycin which downregulate CCR5 receptors thus decreasing CCR5 density. There may even be a role for their use in combination with other entry inhibitors. However, clinical use of CCR5 antagonists may have negative consequences in diseases such as West Nile and Tick-borne encephalitis virus infections. In summary, CCR5 antagonists have great therapeutic potential in the treatment and prevention of HIV as well as future use in novel situations such as organ transplantation. Their optimal use either alone or in combination with other agents will be defined by further investigation.