Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha A.
Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha A.
复制标题
齐多夫定、重组可溶性 CD4 和重组干扰素-α A 三药协同抑制 HIV-1 体外复制。
DOI：
10.1093/infdis/161.6.1059
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发表时间：
1990
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;Barlow,MA;Merrill,DP;Chou,TC;Hirsch,MS
人类免疫缺陷病毒1型（HIV-1）感染的最佳管理可能需要攻击病毒复制周期中不同靶标的药物组合。在体外评价了齐多夫定（AZT）、重组可溶性CD 4（rsCD 4）和重组干扰素-α A（rIFN-αA）在2种和3种药物方案中对HIV-1复制的抑制作用。使用多个HIV-1复制终点研究外周血单核细胞和CD 4 +T细胞系（H9）。药物相互作用采用中效原理和等效线图技术进行评价。AZT、rsCD 4和rIFN-αA在2种和3种药物组合中协同抑制HIV-1。3种药物方案比2种药物方案提供更完全的病毒抑制。在H9细胞中，单一药物方案在10-14天失去效力，2种药物方案在14-18天失去效力。相比之下，3种药物方案在培养28天内显示出几乎完全的抑制，没有毒性。应考虑对这3种药物进行联合临床试验。
Optimal management of human immunodeficiency virus type 1 (HIV-l) infections may require combinations of agents that attack different targets in the viral replicative cycle. Zidovudine (AZT), recombinant soluble CD4 (rsCD4), and recombinant interferon-alpha A (rIFN-αA) were evaluated in 2- and 3-drug regimens against HIV-l replication in vitro. Peripheral blood mononuclear cells and a CD4+T cell line (H9) were studied using multiple HIV-l replicative end points. Drug interactions were evaluated by the median-effect principle and the isobologram technique. AZT, rsCD4, and rIFN-αA inhibited HIV-l synergistically in 2- and 3-drug combinations. The 3-drug regimen provided more complete virus suppression than the 2-drug regimens. In H9 cells, single-drug regimens lost effectiveness at 10–14 days and 2-drug regimens lost effectiveness at 14–18 days. In contrast, the 3-drug regimen showed nearly complete suppression over 28 days in culture without toxicity. Clinical trials of these 3 drugs in combination should be considered.