Rachlis A R
Department of Medicine, Sunnybrook Health Science Centre, Toronto, Ont.
CMAJ. 1990 Dec 1;143(11):1177-85.
Zidovudine (AZT) is the first antiretroviral agent to be licensed for the treatment of human immunodeficiency virus (HIV) infection. Since the initial placebo-controlled trial showing improved survival among patients with acquired immunodeficiency syndrome (AIDS) or symptomatic HIV infection (AIDS-related complex [ARC]) zidovudine has been evaluated in other stages of HIV infection. This review offers physicians who treat patients with HIV infection a comprehensive analysis of the current data on the clinical efficacy of zidovudine in various stages of HIV infection and on zidovudine's adverse effects. After a search of MEDLINE for pertinent articles published since 1985, controlled studies and studies of long-term zidovudine therapy, of zidovudine therapy for HIV-related conditions and of the incidence and management of adverse reactions were evaluated. In addition, abstracts from international meetings were reviewed. No significant difference in clinical outcome was found between high-dose and low-dose zidovudine therapy, but there were significantly fewer toxic effects in the low-dose group. In two other studies zidovudine was found to delay disease progression in patients with asymptomatic or mildly symptomatic HIV infection who had an absolute CD4 count of less than 0.5 x 10(9)/L; the low incidence of adverse reactions may have been due to either the early stage of the infection or the low dose used. The demonstration of zidovudine-resistant isolates after at least 6 months of therapy has yet to be correlated with clinical deterioration. When to begin zidovudine therapy among asymptomatic patients with a CD4 count of less than 0.5 x 10(9)/L remains unclear. Zidovudine can be used safely to delay progression to AIDS or ARC in certain patients with asymptomatic or mildly symptomatic HIV infection and can prolong survival in those with more severe infection. Further studies are necessary to identify indicators that could better define when to start treatment and how to alleviate toxic effects. Combination therapy with such agents as interferon alpha may become the preferred choice of therapy to prevent toxic effects and zidovudine resistance. Zidovudine prophylaxis has been used after HIV exposure. Although studies with animal models have had encouraging results infection has occurred despite immediate prophylaxis and thus further investigation is required.
齐多夫定(AZT)是首个被批准用于治疗人类免疫缺陷病毒(HIV)感染的抗逆转录病毒药物。自最初的安慰剂对照试验显示获得性免疫缺陷综合征(AIDS)或有症状的HIV感染(艾滋病相关综合征[ARC])患者的生存率有所提高以来,齐多夫定已在HIV感染的其他阶段进行了评估。本综述为治疗HIV感染患者的医生提供了关于齐多夫定在HIV感染各阶段的临床疗效及不良反应的当前数据的全面分析。在检索1985年以来发表的相关文章的MEDLINE数据库后,对对照研究、齐多夫定长期治疗研究、HIV相关病症的齐多夫定治疗研究以及不良反应的发生率和管理进行了评估。此外,还查阅了国际会议的摘要。高剂量和低剂量齐多夫定治疗在临床结果上未发现显著差异,但低剂量组的毒性作用明显较少。在另外两项研究中,发现齐多夫定可延缓绝对CD4细胞计数低于0.5×10⁹/L的无症状或轻度症状HIV感染患者的疾病进展;不良反应发生率低可能是由于感染处于早期阶段或使用的剂量较低。治疗至少6个月后出现齐多夫定耐药毒株的情况尚未与临床病情恶化相关联。对于CD4细胞计数低于0.5×10⁹/L的无症状患者何时开始齐多夫定治疗仍不清楚。齐多夫定可安全用于延缓某些无症状或轻度症状HIV感染患者进展为AIDS或ARC,并可延长病情较重患者的生存期。需要进一步研究以确定能更好地界定何时开始治疗以及如何减轻毒性作用的指标。与干扰素α等药物联合治疗可能成为预防毒性作用和齐多夫定耐药的首选治疗方法。HIV暴露后已使用齐多夫定进行预防。尽管动物模型研究取得了令人鼓舞的结果,但尽管立即进行了预防仍发生了感染,因此需要进一步研究。