Eriksson B F, Schinazi R F
Veterans Administration Medical Center Atlanta, Decatur, Georgia 30033.
Antimicrob Agents Chemother. 1989 May;33(5):663-9. doi: 10.1128/AAC.33.5.663.
Combinations of 3'-azido-3'-deoxythymidine and phosphonoformate produced a moderate synergistic inhibitory effect against human immunodeficiency virus type 1 in vitro at concentrations that are easily achieved in humans. The synergistic effect was more pronounced with increasing concentrations and was not secondary to toxic effects of the drugs. 3'-Azido-3'-deoxythymidine neither inhibited the replication of human cytomegalovirus in human embryonic lung fibroblasts nor interfered with the anticytomegalovirus effect of phosphonoformate. By using partially purified reverse transcriptase of human immunodeficiency virus type 1 and human cytomegalovirus DNA polymerase, various combinations of 3'-azido-3'-deoxythymidine-5'-triphosphate and phosphonoformate produced strong indications of additive interactions. The synergistic interactions in infected cells and the additive effects observed at the reverse transcriptase level indicate that mechanisms other than the reverse transcriptase may be of importance for the inhibition of human immunodeficiency virus replication by these two compounds. A concomitant treatment of cytomegalovirus infections, such as cytomegalovirus retinitis, with phosphonoformate in patients with acquired immunodeficiency syndrome receiving 3'-azido-3'-deoxythymidine may be appropriate, and this combination may also be useful in controlling human immunodeficiency virus infection.
在人体易于达到的浓度下，3'-叠氮-3'-脱氧胸苷与膦甲酸盐的组合在体外对1型人类免疫缺陷病毒产生了中等程度的协同抑制作用。随着浓度增加，协同效应更为明显，且并非药物毒性作用所致。3'-叠氮-3'-脱氧胸苷既不抑制人巨细胞病毒在人胚肺成纤维细胞中的复制，也不干扰膦甲酸盐的抗巨细胞病毒效应。通过使用部分纯化的1型人类免疫缺陷病毒逆转录酶和人巨细胞病毒DNA聚合酶，3'-叠氮-3'-脱氧胸苷-5'-三磷酸与膦甲酸盐的各种组合产生了明显的相加相互作用迹象。在感染细胞中的协同相互作用以及在逆转录酶水平观察到的相加效应表明，除逆转录酶外的其他机制可能对这两种化合物抑制1型人类免疫缺陷病毒复制具有重要意义。在接受3'-叠氮-3'-脱氧胸苷治疗的获得性免疫缺陷综合征患者中，用膦甲酸盐同时治疗巨细胞病毒感染，如巨细胞病毒性视网膜炎，可能是合适的，并且这种组合在控制1型人类免疫缺陷病毒感染方面也可能有用。
