Sørensen A M, Nielsen C, Mathiesen L R, Nielsen J O, Hansen J E
Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Denmark.
Scand J Infect Dis. 1993;25(3):365-71. doi: 10.3109/00365549309008512.
3'-azido-3'deoxythymidine (AZT), a clinically used anti-HIV compound, was evaluated for antiviral effect on HIV infection in combination with other antiviral compounds in vitro. Interactions were evaluated by the median-effect principle and the isobologram technique. Synergistic effect was obtained by combining many evaluated antiviral agents with AZT. We observed a difference in the degree of synergism depending on the evaluated compound; the results indicate that compounds with the same target in the viral replicative cycle (ddI: 2',3'-dideoxyinosine, didanosine; d4T: 2',3'-dideoxy-2',3'-didehydrothymidine stavodine; TIBO: tetrahydro-imidazole-benzodiazepin) had a synergistic effect at all concentrations, agents that disturb the infectivity of virus (CAS: Castanospermine; AME: Amphotericin B Methyl Ester) exerted a strong synergistic effect at low concentrations, and finally compounds interfering with the adhesion/penetration process of virus (ConA: Concanavalin A; DS: dextran sulfate) were most potent with AZT when used in rather high concentrations. At this moment in the HIV epidemic, these observations suggest that combinations of antiviral compounds should be evaluated in clinical trials, with the major emphasis on nucleoside analogues and compounds influencing the infectivity of the virus.
3'-叠氮-3'-脱氧胸苷（AZT）是一种临床使用的抗HIV化合物，在体外与其他抗病毒化合物联合使用时，对HIV感染的抗病毒效果进行了评估。通过中位效应原理和等效线图技术评估相互作用。将许多评估的抗病毒药物与AZT联合使用可获得协同效应。我们观察到根据评估的化合物不同，协同程度存在差异；结果表明，在病毒复制周期中具有相同靶点的化合物（ddI：2'，3'-双脱氧肌苷，去羟肌苷；d4T：2'，3'-双脱氧-2'，3'-双脱氢胸苷司他夫定；TIBO：四氢咪唑-苯并二氮杂䓬）在所有浓度下均具有协同效应，干扰病毒感染性的药物（CAS：栗精胺；AME：两性霉素B甲酯）在低浓度时具有很强的协同效应，最后，干扰病毒黏附/穿透过程的化合物（ConA：伴刀豆球蛋白A；DS：硫酸葡聚糖）与AZT联合使用时，在较高浓度下效果最为显著。在当前的HIV疫情形势下，这些观察结果表明，应在临床试验中评估抗病毒化合物的联合使用情况，主要侧重于核苷类似物和影响病毒感染性的化合物。
