IN VITRO INHIBITION OF HIV BY COMBINATION OF MULTIPLE ANTI-HIV AGENTS

多种抗 HIV 药物的组合对 HIV 的体外抑制

• 批准号: 3874494
• 负责人: H MITSUYA
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874494
• 关键词: AIDS; AIDS therapy; CD4 molecule; HIV infections; antiAIDS agent; antiviral agents; combination chemotherapy; cytosine; dextrans; human immunodeficiency virus 1; human subject; inosine; nucleoside analog; virus cytopathogenic effect; zidovudine

We tested the in vitro inhibitory activity of three 2',3'-dideoxynucleosides (ddN) and two viral binding inhibitors in combinations against the infectivity and cytopathic effect of human immunodeficiency virus type 1 (HIV-1). We found that either 3'-azido-2',3'-dideoxythymidine (AZT), 2'3'-dideoxyinosine (ddl), or 2',3'-dideoxycytidine (ddC) combined with soluble recombinant CD4 (sCD4) brings about a synergistic antiretroviral activity without toxicity at clinically achievable concentrations. Combinations of ddNs plus dextran sulfate also exerted similar synergistic antiviral effects without concomitant increases in toxicities. When sCD4 and dextran sulfate were combined, an apparent antagonism was observed. We confirmed that none of the combinations of sCD4 plus AZT, ddl, or ddC exerted significant increase in inhibitory effect on colony formation of human myeloid/ monocytic bone marrow cells in vitro at concentrations used in this study. These data might have a clinical relevance to the treatment of patients with HIV infection.

我们测试了三个化合物的体外抑制活性。 2‘，3’-双脱氧核苷(DDN)和两种病毒结合抑制物 抗人类传染性和细胞病变效应的药物组合 免疫缺陷病毒1型(HIV-1)。我们发现，无论是 3‘-叠氮-2’，3‘-二脱氧胸苷(AZT)，2’3‘-二脱氧肌苷(DDL)，或 2‘，3’-二脱氧胞苷(DdC)与可溶性重组CD_4(SCD_4)结合 在无毒性的情况下产生协同抗逆转录病毒活性 临床上可以达到的浓度。DDNS+右旋糖苷的组合 硫酸盐也有类似的协同抗病毒作用。 随之而来的是毒性的增加。当sCD4和葡聚糖硫酸盐 结合起来，观察到了一种明显的对抗。我们确认没有一个 SCD4+AZT、DDL或ddC的组合显著增加 In对人髓系/单核细胞骨集落形成的抑制作用 在本研究中使用的浓度在体外培养骨髓细胞。这些数据 可能对艾滋病患者的治疗有临床意义 感染。