Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard St, Baltimore, 21201 Maryland, USA.
J Transl Med. 2011 Jan 27;9 Suppl 1(Suppl 1):S9. doi: 10.1186/1479-5876-9-S1-S9.
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.
自 CCR5 被发现作为 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。尽管已经有几种 CCR5 拮抗剂在临床试验中进行了评估，但只有马拉维若在治疗 HIV 感染患者方面被批准临床使用。本文回顾了 CCR5 拮抗剂的疗效、安全性和耐药性概况，重点介绍了马拉维若，以及它们在特殊和新兴临床情况下的应用。尽管马拉维若自 2007 年以来已获准使用，但在 HIV 治疗中以及在其他疾病中的最佳使用尚未得到很好的定义。马拉维若和其他 CCR5 拮抗剂有可能在其他多种临床情况下使用，例如预防 HIV 传播、强化 HIV 治疗和预防器官移植排斥反应。CCR5 拮抗剂的使用可能会受到其他药物的增强，如雷帕霉素，它可以下调 CCR5 受体，从而降低 CCR5 密度。甚至可能需要将其与其他进入抑制剂联合使用。然而，在西尼罗河和蜱传脑炎病毒感染等疾病中，使用 CCR5 拮抗剂可能会产生负面影响。总之，CCR5 拮抗剂在治疗和预防 HIV 方面具有很大的治疗潜力，未来在器官移植等新情况下也有应用前景。无论是单独使用还是与其他药物联合使用，其最佳使用方式将通过进一步研究来确定。
