Davey R T, Boenning C M, Herpin B R, Batts D H, Metcalf J A, Wathen L, Cox S R, Polis M A, Kovacs J A, Falloon J
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Infect Dis. 1994 Nov;170(5):1180-8. doi: 10.1093/infdis/170.5.1180.
Single and multiple doses of sCD4-PE40, a soluble recombinant fusion toxin selectively toxic to gp120-expressing cells, were evaluated in persons infected with human immunodeficiency virus type 1 (HIV-1). Seventeen of 24 patients who completed a single-dose safety trial were given either 1, 5, 10, or 15 micrograms/kg of sCD4-PE40 by intravenous bolus once a month for 2 months, then weekly for 6 weeks. The weekly maximally tolerated dose was 10 micrograms/kg. The major toxicity was a transient dose-dependent elevation in hepatic aminotransferases peaking 48 h after infusion. Anti-Pseudomonas exotoxin antibody developed in 58% of recipients, and sera from 13 of 17 showed neutralizing activity against sCD4-PE40. No consistent changes in immunologic or virologic markers were observed. Weekly infusions of < or = 10 micrograms/kg of sCD4-PE40 are generally well tolerated, but additional studies correlating optimal dosing and frequency of administration with efficacy will be needed to define the role of this novel agent in the management of HIV-1-infected patients.
对一种对表达gp120的细胞具有选择性毒性的可溶性重组融合毒素sCD4-PE40进行了单剂量和多剂量评估，受试对象为1型人类免疫缺陷病毒（HIV-1）感染者。在完成单剂量安全性试验的24名患者中，17名患者每月静脉推注1、5、10或15微克/千克的sCD4-PE40，共2个月，之后每周1次，持续6周。每周的最大耐受剂量为10微克/千克。主要毒性为输注后48小时达到峰值的肝转氨酶短暂性剂量依赖性升高。58%的受试者产生了抗铜绿假单胞菌外毒素抗体，17名受试者中有13名的血清显示出对sCD4-PE40的中和活性。未观察到免疫或病毒学标志物的一致变化。每周输注≤10微克/千克的sCD4-PE40通常耐受性良好，但需要进一步研究以确定最佳给药剂量和频率与疗效之间的关系，从而明确这种新型药物在HIV-1感染患者治疗中的作用。
