Human immunodeficiency virus type 1 (HIV-1) inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2',3'-dideoxycytidine, or recombinant interferon-alpha A against zidovudine-sensitive or -resistant HIV-1 in vitro.
Human immunodeficiency virus type 1 (HIV-1) inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2',3'-dideoxycytidine, or recombinant interferon-alpha A against zidovudine-sensitive or -resistant HIV-1 in vitro.
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人类免疫缺陷病毒 1 型 (HIV-1) 蛋白酶抑制剂 Ro 31-8959 与齐多夫定、2,3-双脱氧胞苷或重组干扰素-α A 之间在体外对齐多夫定敏感或耐药的 HIV-1 的抑制相互作用。
DOI：
10.1093/infdis/166.5.1143
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Hirsch,MS
中科院分区：
文献类型：
--
作者：
Johnson,VA;Merrill,DP;Chou,TC;Hirsch,MS
蛋白酶抑制剂 Ro 31-8959 是一种可中断人类免疫缺陷病毒 (HIV) 特异性感染性病毒颗粒形成的化合物，在与齐多夫定、2',3'-二脱氧胞苷 (ddC) 或重组干扰素-αA (rIFN-αA) 联合使用的双药方案中对 HIV-1 复制的体外抑制作用进行了评估。利用感染HIV-1的外周血单核细胞，采用中效原理和等效线图技术评价药物相互作用。研究了齐多夫定敏感且耐药的 HIV-1 分离株对。 7.5–30 nMRo 31-8959 和 0.005–0.02 µMzidovudine（对于齐多夫定敏感的 HIV-1 分离株）、0.25–1.0 µMzidovudine（对于齐多夫定耐药的 HIV-1 分离株）、0.025–0.1 µMddC 和8–32 单位/mL，rIFN-αA，无附加毒性。 Ro 31-8959治疗HIV-1感染的I/II期临床试验正在进行中。如果结果良好，包括 Ro 31-8959 在内的联合治疗方案值得考虑用于未来的临床试验。
Protease inhibitor Ro 31-8959, a compound that interrupts human immunodeficiency virus (HIV)-specific formation of infectious virions, was evaluated in two-drug combined regimens with zidovudine, 2′,3′-dideoxycytidine (ddC), or recombinant interferon-αA (rIFN-αA) against HIV-1 replication in vitro. By using peripheral blood mononuclear cells infected with HIV-1, drug interactions were evaluated by the median-effect principle and the isobologram technique. A zidovudine-sensitive and -resistant HIV-1 isolate pair was studied. Additive to synergistic anti-HIV-1 interactions were seen with 7.5–30 nMRo 31-8959 and 0.005–0.02 µMzidovudine (for the zidovudine-sensitive HIV-1 isolate), 0.25–1.0 µMzidovudine (for the zidovudine-resistant HIV-1 isolate), 0.025–0.1 µMddC, and 8–32 units/mL, rIFN-αA, without additive toxicity. Phase I/II clinical trials of Ro 31-8959 for therapy of HIV-1 infection are in progress. if results are favorable, combined regimens including Ro 31-8959 deserve consideration for future clinical trials.