Institute of Virology, University of Cologne, Cologne, Germany.
Intervirology. 2012;55(2):84-97. doi: 10.1159/000331995. Epub 2012 Jan 24.
Inhibition of HIV replication initially targeted viral enzymes, which are exclusively expressed by the virus and not present in the human cell. The development of reverse transcriptase (RT) inhibitors started with the discovery of antiretroviral activity of the nucleoside analog zidovudine in March 1987. Currently, six major classes of antiretroviral drugs are used for the treatment of HIV-infected patients: the RT inhibitors, nucleoside inhibitors and nonnucleoside inhibitors, the protease inhibitors, the integrase inhibitor raltegravir, the fusion inhibitor enfuvirtide (T-20), and the chemokine receptor 5 antagonist maraviroc. A seventh class, the maturation inhibitors, has not yet been approved as their effectiveness is impaired by HIV-1 polymorphisms naturally occurring in 30-40% of HIV-1 therapy-naive isolates. The use of antiretroviral combination therapy has proven to be effective in delaying progression to AIDS and to reconstitute the immune system of HIV-infected individuals. During the last 5 years, the introduction of the newest antiretrovirals has increased treatment efficacy tremendously. However, the development and accumulation of resistance to all antiretroviral drug classes are still a major problem. Additional targets will have to be defined to achieve the ultimate goal: the eradication of the virus from the infected human body.
HIV 复制的最初抑制靶点是病毒特有的酶,而这些酶并不存在于人类细胞中。逆转录酶 (RT) 抑制剂的开发始于 1987 年 3 月发现核苷类似物齐多夫定具有抗逆转录病毒活性。目前,有六种主要类别的抗逆转录病毒药物用于治疗 HIV 感染患者:逆转录酶抑制剂、核苷抑制剂和非核苷抑制剂、蛋白酶抑制剂、整合酶抑制剂拉替拉韦、融合抑制剂恩夫韦肽(T-20)和趋化因子受体 5 拮抗剂马拉维若。第七类,成熟抑制剂,尚未获得批准,因为它们的有效性受到 HIV-1 天然存在于 30-40%的 HIV-1 治疗初治分离株中的多态性的影响。抗逆转录病毒联合治疗已被证明可有效延缓艾滋病的进展,并重建 HIV 感染者的免疫系统。在过去的 5 年中,新型抗逆转录病毒药物的引入极大地提高了治疗效果。然而,所有抗逆转录病毒药物类别的耐药性的发展和积累仍然是一个主要问题。需要定义其他靶点,以实现最终目标:从受感染人体中消除病毒。