Klibanov Olga M
Wingate University School of Pharmacy, Wingate, NC 28174-0159, USA.
Curr Opin Investig Drugs. 2009 Aug;10(8):845-59.
Highly active antiretroviral therapy has revolutionized the care of patients with HIV infection, but treatment is often complicated by the development of antiretroviral resistance. CCR5 inhibitors are a novel class of antiretroviral agents that block the CCR5 receptor, thereby preventing HIV-1 recognition and entry into CD4+ macrophages and T-cells. Schering-Plough Corp is developing vicriviroc, a CCR5 inhibitor that has demonstrated good oral bioavailability, has a long half-life that allows once daily dosing, and is primarily metabolized by cytochrome P450 CYP3A4. In vitro and clinical data suggest that vicriviroc has excellent antiviral potency with minimal toxicity. Phase I and II clinical trials demonstrated promising efficacy results when vicriviroc is administered to patients infected with CCR5-tropic HIV-1. At the time of publication, phase III trials were ongoing or planned to investigate the efficacy and safety of vicriviroc in antiretroviral-naïve and -experienced patients infected with HIV-1.
高效抗逆转录病毒疗法彻底改变了对HIV感染患者的治疗，但治疗常常因抗逆转录病毒耐药性的出现而变得复杂。CCR5抑制剂是一类新型抗逆转录病毒药物，可阻断CCR5受体，从而防止HIV-1识别并进入CD4+巨噬细胞和T细胞。先灵葆雅公司正在研发vicriviroc，这是一种CCR5抑制剂，已证明其具有良好的口服生物利用度，半衰期长，允许每日给药一次，并且主要通过细胞色素P450 CYP3A4代谢。体外和临床数据表明，vicriviroc具有出色的抗病毒效力且毒性极小。I期和II期临床试验表明，将vicriviroc给予感染CCR5嗜性HIV-1的患者时，疗效结果令人期待。在撰写本文时，III期试验正在进行或计划开展，以研究vicriviroc在初治和经治HIV-1感染患者中的疗效和安全性。
