Daar E S, Ho D D
Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine.
Am J Med. 1991 Apr 10;90(4A):22S-26S. doi: 10.1016/0002-9343(91)90407-o.
Replication of the human immunodeficiency virus type 1 (HIV-1) underlies the pathogenesis and progression of the acquired immunodeficiency syndrome (AIDS). A soluble form of the virus receptor, CD4, has been developed as a potential therapeutic agent with good activity against laboratory strains of HIV-1 in vitro. However, quantitative virologic studies performed to date on the blood of patients receiving recombinant soluble CD4 (sCD4) demonstrated no efficacy in vivo despite good drug levels in serum. These results led us to examine the neutralizing activity of sCD4 against multiple primary HIV-1 isolates from infected patients. The findings demonstrate that primary isolates were significantly more resistant to sCD4 than were laboratory strains, which suggests a need to reevaluate CD4-based therapies and to conduct better designed preclinical studies that include experiments performed on patient viral isolates.
人类免疫缺陷病毒1型（HIV-1）的复制是获得性免疫缺陷综合征（AIDS）发病机制和病情进展的基础。一种可溶性形式的病毒受体CD4已被开发为一种潜在的治疗药物，在体外对HIV-1实验室菌株具有良好的活性。然而，迄今为止，对接受重组可溶性CD4（sCD4）治疗患者的血液进行的定量病毒学研究表明，尽管血清中的药物水平良好，但sCD4在体内并无疗效。这些结果促使我们检测sCD4对来自感染患者的多种HIV-1原始分离株的中和活性。研究结果表明，原始分离株对sCD4的耐药性明显高于实验室菌株，这表明有必要重新评估基于CD4的治疗方法，并开展设计更合理的临床前研究，包括对患者病毒分离株进行的实验。
