Ramachandran R V, Katzenstein D A, Wood R, Batts D H, Merigan T C
Center for AIDS Research, Stanford University Medical Center, California 94305.
J Infect Dis. 1994 Oct;170(4):1009-13. doi: 10.1093/infdis/170.4.1009.
The safety, immunologic, and antiviral effects of a recombinant biologic product that combines the second and third domains of the CD4 molecule and Pseudomonas exotoxin A (PE40) were evaluated in 21 human immunodeficiency virus (HIV)-infected subjects in a phase III open-label dose-ranging study. Subjects with CD4+ lymphocyte counts of 100-500/mm3 received CD4-PE40 at 40, 80, or 160 micrograms/m2 by infusion three to seven times over 10 days. At the maximum tolerated dose (80 micrograms/m2), peak CD4-PE40 levels were 65-130 ng/mL with a serum half-life of 3.6 +/- 1.5 h. Toxicity, primarily increased hepatic transaminases, was dose-related and reversible. HIV DNA proviral levels in peripheral blood mononuclear cells and plasma HIV RNA remained stable during and after CD4-PE40 infusions. The relative resistance of clinical isolates of HIV, limits of the tolerated dose, and the immunogenicity and short half-life of the protein may explain the lack of in vivo antiviral effect of CD4-PE40.
在一项III期开放标签剂量范围研究中，对21名人类免疫缺陷病毒（HIV）感染受试者评估了一种重组生物制品的安全性、免疫和抗病毒作用，该制品结合了CD4分子的第二和第三结构域以及铜绿假单胞菌外毒素A（PE40）。CD4 +淋巴细胞计数为100 - 500/mm3的受试者在10天内通过输注接受3至7次剂量为40、80或160微克/平方米的CD4-PE40。在最大耐受剂量（80微克/平方米）时，CD4-PE40峰值水平为65 - 130纳克/毫升，血清半衰期为3.6±1.5小时。毒性主要为肝转氨酶升高，与剂量相关且可逆。在CD4-PE40输注期间及之后，外周血单核细胞中的HIV DNA原病毒水平和血浆HIV RNA保持稳定。HIV临床分离株的相对抗性、耐受剂量的限制以及该蛋白的免疫原性和短半衰期可能解释了CD4-PE40缺乏体内抗病毒作用的原因。
