Inhibition of human immunodeficiency virus type 1 replication in cytokine-stimulated monocytes/macrophages by combination therapy.

Inhibition of human immunodeficiency virus type 1 replication in cytokine-stimulated monocytes/macrophages by combination therapy.
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通过联合疗法抑制细胞因子刺激的单核细胞/巨噬细胞中人类免疫缺陷病毒 1 型复制。

DOI:
10.1093/infdis/170.6.1361
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发表时间:
1994
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Hirsch,MS
Hirsch,MS
中科院分区:
--
文献类型:
--
作者:
Rusconi,S;Merrill,DP;Hirsch,MS

文献摘要

被引文献

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在粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 刺激的单核细胞/巨噬细胞培养物中研究了针对人类免疫缺陷病毒 1 型 (HIV-1) 的联合治疗方案。治疗方案包括抑制相同靶标(逆转录酶)或多个靶标的方案。治疗条件评估预防和持续感染期间的疗效。药物包括齐多夫定、去羟肌苷、奈韦拉平、膦甲酸、吡啶酮、蛋白酶抑制剂 R031-8959(也称为沙奎那韦)、干扰素-αA、Tat 抑制剂 RO24-7429 和 N-丁基脱氧野尻霉素。测试了两种、三种和四种药物的组合。药物在 IC99、IC95、IC75 和 IC50 的单独抑制浓度下进行测试。所有预防方案均能在 IC99 时阻止 HIV-1 复制。随着药物浓度的降低,治疗方案之间的差异变得明显。针对单一和多个目标的治疗方案在预防环境中有效,但在急性感染中效果较差。在持续感染中,即使在 IC99 下,也仅观察到病毒复制的适度减少。
Combination regimens against human immunodeficiency virus type 1 (HIV-1) werestudied in granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated monocyte/macrophage cultures. Regimens included those that inhibited the same target (reverse transcriptase) or multiple targets. Treatment conditions assessed efficacy during prophylaxis and ongoing infection. Drugs included zidovudine, didanosine, nevirapine, foscarnet, pyridinone, the protease inhibitor R031–8959 (also known as saquinavir), interferon-αA, the Tat inhibitor RO24–7429, andN-butyl-deoxynojirimycin. Two-, three-, and four-drug combinations were tested. Drugs were tested at individually inhibitory concentrations of IC99, IC95, IC75, and IC50. All prophylactic regimens prevented HIV-1 replication at IC99. As drug concentrations were reduced, differences among the regimens became apparent. Regimens that acted at both single and multiple targets were effective in prophylactic settings and less so in acute infection. In ongoing infections, only modest reductions in viral replication were seen, even at IC99.