Hartley Oliver, Martins Elsa, Scurci Ilaria
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Switzerland.
Swiss Med Wkly. 2018 Jan 26;148:w14580. doi: 10.4414/smw.2018.14580. eCollection 2018.
Of the two million people estimated to be newly infected with human immunodeficiency virus (HIV) every year, 95% live in poorer regions of the world where effective HIV treatment is not universally available. Strategies to reduce the spread of HIV infection, which predominantly occurs via sexual contact, are urgently required. In the absence of an effective vaccine, a number of approaches to prevent HIV infection have been developed. These include using potent anti-HIV drugs prophylactically, either through systemic administration or topical application to the mucosal tissues that HIV initially encounters during sexual transmission. Genetic deficiency of the chemokine receptor CCR5 provides individuals with a remarkable degree of protection from HIV acquisition. This is because CCR5 is the major coreceptor used by HIV to infect new target cells. Since CCR5 deficiency does not appear to carry any health disadvantages, targeting the receptor is a promising strategy for both therapy and prevention of HIV. In this review we first describe the advantages and limitations of the currently available strategies for HIV prevention, then we focus on strategies targeting CCR5, covering the progress that has been made in developing different classes of CCR5 inhibitors for prophylaxis, and the perspectives for their future development as new weapons in the global fight against HIV/AIDS.
据估计，每年有200万人新感染人类免疫缺陷病毒（HIV），其中95%生活在世界较贫困地区，这些地区无法普遍获得有效的HIV治疗。迫切需要采取策略来减少主要通过性接触传播的HIV感染。在缺乏有效疫苗的情况下，已经开发出多种预防HIV感染的方法。这些方法包括预防性使用强效抗HIV药物，既可以通过全身给药，也可以局部应用于HIV在性传播过程中最初接触的黏膜组织。趋化因子受体CCR5的基因缺陷为个体提供了显著程度的预防HIV感染的保护。这是因为CCR5是HIV用来感染新靶细胞的主要共受体。由于CCR5缺陷似乎不会带来任何健康劣势，针对该受体是治疗和预防HIV的一种有前景的策略。在本综述中，我们首先描述当前可用的HIV预防策略的优缺点，然后重点关注针对CCR5的策略，涵盖开发不同类别的CCR5抑制剂用于预防方面所取得的进展，以及它们作为全球抗击HIV/AIDS新武器的未来发展前景。
