Merigan T C
Division of Infectious Diseases, Stanford University School of Medicine, California 94305.
Am J Med. 1991 Apr 10;90(4A):8S-17S. doi: 10.1016/0002-9343(91)90405-m.
Although 3'-azido-3'-deoxythymidine (zidovudine, AZT) has demonstrated efficacy in the treatment of human immunodeficiency virus (HIV) infection, there are limitations associated with its use. Consequently, other agents, such as 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI), are being assessed for the treatment of patients with HIV infection. However, the most effective therapy for HIV infection may be combination therapy with zidovudine and any of a number of other therapies. To obtain maximum efficacy, combination regimens should include agents that do not share cross-resistance, have different mechanisms of action, and have different dose-limiting toxicities; the relative merits of a concurrent dosage schedule (limits drug failure) and a consecutive dosage schedule (limits toxicity) must also be considered. In addition, the shift between administering a starting regimen and a rescue regimen should be based on time on therapy, disease breakthrough, or drug complication. Eventually, the shift may be precipitated by the in vitro resistance patterns of individual viruses, as is now the case with antibiotics for infection. Several trials are currently in progress to assess combination therapy with zidovudine and ddC; initial results indicate that the combination may allow for improved efficacy and decreased side effects, compared with treatment with either drug alone. Trials of combination therapy with ddI, interferon alfa, and acyclovir are also in progress. It is hoped that these initial studies will pave the way for rational drug sequencing in the treatment of patients with acquired immunodeficiency syndrome.
尽管3'-叠氮-3'-脱氧胸苷（齐多夫定，AZT）已证明在治疗人类免疫缺陷病毒（HIV）感染方面有效，但其使用存在局限性。因此，正在评估其他药物，如2'，3'-双脱氧胞苷（ddC）和2'，3'-双脱氧肌苷（ddI）用于治疗HIV感染患者。然而，治疗HIV感染最有效的疗法可能是齐多夫定与许多其他疗法中的任何一种联合使用。为了获得最大疗效，联合用药方案应包括不具有交叉耐药性、作用机制不同且剂量限制性毒性不同的药物；还必须考虑同时给药方案（限制药物失效）和连续给药方案（限制毒性）的相对优点。此外，从起始治疗方案转换为挽救治疗方案应基于治疗时间、疾病突破或药物并发症。最终，这种转换可能由个别病毒的体外耐药模式引发，就像目前治疗感染使用抗生素的情况一样。目前正在进行多项试验以评估齐多夫定与ddC的联合治疗；初步结果表明，与单独使用任何一种药物治疗相比，联合用药可能提高疗效并减少副作用。ddI、干扰素α和阿昔洛韦联合治疗的试验也在进行中。希望这些初步研究将为获得性免疫缺陷综合征患者的合理药物排序铺平道路。
