A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection
A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection
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DOI：
10.1086/515312
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发表时间：
1998-06-01
影响因子：
6.4
通讯作者：
Ho, DD
中科院分区：
文献类型：
--
作者：
Markowitz, M;Conant, M;Ho, DD
一项评价甲磺酸奈非那韦安全性、药代动力学和抗病毒活性的I/II期剂量范围开放标签28天单药治疗研究（Viracept），一种人类免疫缺陷病毒（HIV）-1蛋白酶的抑制剂，在65名HIV-1感染的受试者中进行。28天后，54名受试者参加了一个开放的-标签扩展允许添加逆转录酶核苷抑制剂和剂量递增以维持持久性。该药物耐受性良好，表现出强大的抗病毒活性，750 mg和1000 mg每日三次方案具有明显的优效性。30名在12个月时继续接受治疗的受试者HIV RNA持续下降1.6 log（10），同时CD 4细胞平均增加180-200/mm（3）。病毒反弹后的病毒基因型和表型研究显示，允许奈非那韦耐药的初始活性位点突变是由HIV-1蛋白酶D30 N中的独特氨基酸取代介导的，其不会赋予对目前可用的蛋白酶抑制剂的体外表型交叉耐药性。
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-l-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 log(10) reduction in HIV RNA, accompanied by a mean increase in CD4 cells of 180-200/mm(3). 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.