Markowitz M, Conant M, Hurley A, Schluger R, Duran M, Peterkin J, Chapman S, Patick A, Hendricks A, Yuen G J, Hoskins W, Clendeninn N, Ho D D
Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 10016, USA.
J Infect Dis. 1998 Jun;177(6):1533-40. doi: 10.1086/515312.
A phase I/II dose-ranging open-label 28-day monotherapy study of the safety, pharmacokinetics, and antiviral activity of nelfinavir mesylate (Viracept), an inhibitor of human immunodeficiency virus (HIV)-1 protease, was done in 65 HIV-1-infected subjects. After 28 days, 54 responding subjects entered an open-label extension that allowed for the addition of nucleoside inhibitors of reverse transcriptase and dose escalation to maintain durability. The drug was well-tolerated and demonstrated robust antiviral activity, with demonstrable superiority of the 750 mg and 1000 mg three times daily regimens. Thirty subjects who continued to receive therapy at 12 months attained a persistent 1.6 log10 reduction in HIV RNA, accompanied by a mean increase in CD4 cells of 180-200/mm3. Studies of viral genotype and phenotype after virus rebound revealed that the initial active site mutation allowing for nelfinavir resistance is mediated by a unique amino acid substitution in the HIV-1 protease D30N, which does not confer in vitro phenotypic cross-resistance to the currently available protease inhibitors.
一项关于甲磺酸奈非那韦（Viracept，一种人类免疫缺陷病毒（HIV）-1蛋白酶抑制剂）安全性、药代动力学及抗病毒活性的I/II期剂量范围开放标签28天单药治疗研究在65名HIV-1感染受试者中开展。28天后，54名有反应的受试者进入开放标签扩展期，在此期间可添加逆转录酶核苷抑制剂并增加剂量以维持疗效。该药物耐受性良好，并显示出强大的抗病毒活性，每日三次750毫克和1000毫克方案具有明显优势。30名在12个月时继续接受治疗的受试者HIV RNA持续降低1.6 log10，同时CD4细胞平均增加180 - 200/mm3。病毒反弹后对病毒基因型和表型的研究表明，导致奈非那韦耐药的初始活性位点突变由HIV-1蛋白酶D30N中独特的氨基酸取代介导，该突变不会赋予对目前可用蛋白酶抑制剂的体外表型交叉耐药性。
