D'Souza M P, Cairns J S, Plaeger S F
Vaccine Clinical Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4152, 6700-B Rockledge Dr, Bethesda, MD 20892, USA.
JAMA. 2000 Jul 12;284(2):215-22. doi: 10.1001/jama.284.2.215.
Great strides have been made in developing potent antiretroviral regimens that block human immunodeficiency virus (HIV) transcription and assembly. Despite these therapeutic advances, problems of drug resistance, latent viral reservoirs, and drug-induced toxic effects that compromise effective viral control point to the need for new classes of anti-HIV drugs with different modes of action. One promising approach involves blocking HIV entry into human cells, a complex process that involves multiple protein interactions. The process of HIV entry begins with binding of the viral envelope glycoprotein to both the CD4 receptor and one of several chemokine receptors and ends with fusion of viral and cell membranes. Conceptually, there are 3 steps in the HIV entry process that could serve as therapeutic targets: binding of the viral envelope glycoprotein with the CD4 receptor, binding of the envelope-CD4 complex to chemokine receptors, and fusion of the viral and cell membranes. Preclinical and clinical assessment of these entry inhibitors is ongoing and will determine if they possess properties required for drug licensure. Moreover, the worldwide epidemic is largely occurring in developing countries that cannot afford these drugs: a prophylactic vaccine is necessary and urgent. New knowledge of the HIV-envelope glycoprotein has also provided insight into possibilities for the design of novel HIV vaccines. JAMA. 2000;284:215-222
在开发能阻断人类免疫缺陷病毒（HIV）转录和组装的强效抗逆转录病毒疗法方面已经取得了巨大进展。尽管有这些治疗上的进步，但耐药性、潜伏病毒库以及影响有效病毒控制的药物诱导毒性作用等问题表明，需要有具有不同作用方式的新型抗HIV药物。一种有前景的方法是阻断HIV进入人体细胞，这是一个涉及多种蛋白质相互作用的复杂过程。HIV进入过程始于病毒包膜糖蛋白与CD4受体以及几种趋化因子受体之一的结合，结束于病毒膜与细胞膜的融合。从概念上讲，HIV进入过程中有3个步骤可作为治疗靶点：病毒包膜糖蛋白与CD4受体的结合、包膜-CD4复合物与趋化因子受体的结合以及病毒膜与细胞膜的融合。这些进入抑制剂的临床前和临床评估正在进行中，将确定它们是否具备药物许可所需的特性。此外，全球范围内的疫情主要发生在买不起这些药物的发展中国家：预防性疫苗是必要且紧迫的。对HIV包膜糖蛋白的新认识也为设计新型HIV疫苗提供了思路。《美国医学会杂志》。2000年；284:215 - 222
