Fischl M A
Department of Medicine, University of Miami School of Medicine, Florida 33101.
Am J Med. 1991 Apr 10;90(4A):2S-7S. doi: 10.1016/0002-9343(91)90404-l.
In vitro studies have shown that 3'-azido-3'-deoxythymidine (zidovudine, AZT) and interferon synergistically inhibit the replication of the human immunodeficiency virus type 1 (HIV) in peripheral blood mononuclear cells at concentrations achievable in patients. Interferon alfa can cause lesions to regress in patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). Although zidovudine has no significant effect on the regression of these lesions, it does have antiviral activity in these patients as manifested by a decline in serum HIV antigen. However, when used separately, the two drugs can have serious side effects in some patients. In addition, the development of zidovudine-resistant strains has been noted in patients with advanced HIV disease receiving zidovudine for nine months or longer. Three in vivo trials have been initiated to assess possible advantages of combination therapy with zidovudine and interferon alfa in patients with AIDS-related KS. The incidence of serious adverse reactions, therapeutic efficacy, and the rate of emergence of zidovudine-resistant strains of HIV were evaluated. Preliminary results indicate that combination therapy with interferon alfa and zidovudine can safely be administered to patients with AIDS-related KS in doses that elicit antitumor and antiviral responses and discourage the potential emergence of zidovudine-resistant HIV strains.
体外研究表明，3'-叠氮-3'-脱氧胸苷（齐多夫定，AZT）与干扰素在患者可达到的浓度下协同抑制外周血单核细胞中1型人类免疫缺陷病毒（HIV）的复制。α干扰素可使获得性免疫缺陷综合征（AIDS）相关的卡波西肉瘤（KS）患者的病变消退。尽管齐多夫定对这些病变的消退无显著作用，但在这些患者中它确实具有抗病毒活性，表现为血清HIV抗原下降。然而，单独使用时，这两种药物在一些患者中会产生严重的副作用。此外，接受齐多夫定治疗9个月或更长时间的晚期HIV疾病患者中已发现齐多夫定耐药毒株的出现。已启动三项体内试验，以评估齐多夫定与α干扰素联合治疗对AIDS相关KS患者可能的优势。评估了严重不良反应的发生率、治疗效果以及HIV齐多夫定耐药毒株的出现率。初步结果表明，α干扰素与齐多夫定联合治疗可以安全地给予AIDS相关KS患者，剂量可引发抗肿瘤和抗病毒反应，并抑制齐多夫定耐药HIV毒株的潜在出现。
