Harrington P T
University of Florida Health Science Center, Jacksonville.
J Fla Med Assoc. 1991 Oct;78(10):664-8.
The natural history of HIV infection continues to change with improved diagnostic and therapeutic modalities available to manage opportunistic infections and malignancies. Antiretroviral therapy with zidovudine and other investigational agents has improved the median survival of AIDS patients from 11 months in 1985 to 18-25 months at present. Most importantly, early intervention with zidovudine can delay onset of clinical illness in asymptomatic patients and progression to AIDS in symptomatic patients. A 500 mg/d dose has been found as effective as previously recommended doses of 1200-1500 mg/day. Lower doses decrease the incidence and severity of adverse effects and therapeutic benefit appears to be greatest in asymptomatic patients with CD4 lymphocyte counts less than 500/ul. Indications for zidovudine, therefore, have been expanded to include asymptomatic adults with CD4 lymphocyte counts less than 500/ul. Concerning early intervention with zidovudine, studies were not designed to measure survival or define the optimal timing of intervention based on immunologic status. In addition, long-term benefits are not clearly defined, particularly since the drug seems to lose clinical effectiveness after approximately two years, probably due to emergence of resistant HIV strains. Adverse effects continue to occur even at low doses including headaches, nausea, anemia and neutropenia, myopathy and possible hepatitis. Nevertheless, the overall clinical benefit seems to be greatest, albeit temporary, in asymptomatic patients. The optimal dosage appears to be 500-600 mg/d; however, this may not be sufficient for infection in the central nervous system.
随着用于治疗机会性感染和恶性肿瘤的诊断和治疗方式的改进,HIV感染的自然史也在不断变化。齐多夫定和其他研究性药物的抗逆转录病毒疗法已将艾滋病患者的中位生存期从1985年的11个月提高到目前的18 - 25个月。最重要的是,对齐多夫定的早期干预可以延缓无症状患者临床疾病的发作,并延缓有症状患者发展为艾滋病。已发现500毫克/天的剂量与先前推荐的1200 - 1500毫克/天的剂量一样有效。较低剂量可降低不良反应的发生率和严重程度,且治疗益处似乎在CD4淋巴细胞计数低于500/微升的无症状患者中最大。因此,齐多夫定的适应证已扩大到包括CD4淋巴细胞计数低于500/微升的无症状成年人。关于齐多夫定的早期干预,研究并非旨在测量生存期或根据免疫状态确定最佳干预时机。此外,长期益处尚不明确,特别是因为该药物似乎在大约两年后失去临床疗效,可能是由于耐药HIV毒株的出现。即使是低剂量,不良反应仍会发生,包括头痛、恶心、贫血和中性粒细胞减少、肌病以及可能的肝炎。然而,总体临床益处似乎在无症状患者中最大,尽管是暂时的。最佳剂量似乎是500 - 600毫克/天;然而,这可能不足以治疗中枢神经系统感染。