Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase I-II escalating dosage trial.
Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase I-II escalating dosage trial.
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DOI：
10.7326/0003-4819-112-4-247
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发表时间：
1990-02
影响因子：
39.2
通讯作者：
R. Schooley;T. Merigan;P. Gaut;M. Hirsch;M. Holodniy;T. Flynn;S. Liu;R. Byington;S. Henochowicz;E. Gubish
中科院分区：
文献类型：
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作者：
R. Schooley;T. Merigan;P. Gaut;M. Hirsch;M. Holodniy;T. Flynn;S. Liu;R. Byington;S. Henochowicz;E. Gubish
研究目的研究重组可溶性CD 4（rsCD 4）治疗获得性免疫缺陷综合征（AIDS）和晚期AIDS相关综合征的安全性和药代动力学，并初步寻找疗效的替代指标。设计开放标签、剂量递增、I-II期耐受性试验。设置马萨诸塞州总医院，雪松西奈医学中心，和斯坦福大学医学院，三个三级保健机构和国家过敏和传染病研究所艾滋病临床试验组的成员。3至11名患者的队列通过静脉输注或肌肉注射接受rsCD 4，剂量高达30 mg/天，持续28天。测量和主要结果重组可溶性CD 4被这些患者耐受，没有显著的临床或免疫毒性。接受9或30 mg/天肌内给药的患者的血清rsCD 4水平在体外抑制人类免疫缺陷病毒1（HIV-1）复制所需的rsCD 4浓度范围内。在每天接受30 mg rsCD 4的患者中观察到血清HIV-1 p24抗原下降，但在较低剂量下未观察到此类变化。结论重组可溶性CD 4在AIDS或晚期AIDS相关综合征患者中具有良好的耐受性。我们的研究也为rsCD 4的体内抗病毒活性提供了初步证据。我们的数据表明，进一步试验的受体为基础的治疗艾滋病毒-1是必要的。
STUDY OBJECTIVE To study the safety and pharmacokinetics and to derive preliminary evidence on surrogate indicators of efficacy of recombinant soluble CD4 (rsCD4) in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex. DESIGN Open label, escalating dosage, phase I-II tolerance trial. SETTING Massachusetts General Hospital, Cedars-Sinai Medical Center, and Stanford University Medical School, three tertiary care institutions and members of the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. INSTRUCTIONS Cohorts of 3 to 11 patients received rsCD4 by intravenous infusion or intramuscular injection in dosages of up to 30 mg per day for 28 days. MEASUREMENTS AND MAIN RESULTS Recombinant soluble CD4 was tolerated by these patients with no significant clinical or immunologic toxicities. Serum levels of rsCD4 in patients receiving doses of 9 or 30 mg per day administered intramuscularly were in the range of rsCD4 concentrations required to inhibit replication of human immunodeficiency virus 1 (HIV-1) in vitro. A decline in serum HIV-1 p24 antigen was seen in patients receiving 30 mg of rsCD4 daily, but no such changes were noted at lower dosages. CONCLUSIONS Recombinant soluble CD4 is well tolerated by patients with AIDS or advanced AIDS-related complex. Our study has also provided preliminary evidence of antiviral activity of rsCD4 in vivo. Our data suggest that further trials of receptor-based therapies against HIV-1 are warranted.