Portegies P
Academic Medical Centre, University of Amsterdam, The Netherlands.
Drugs. 1995;49 Suppl 1:25-31; discussion 38-40. doi: 10.2165/00003495-199500491-00007.
Following the introduction of zidovudine, a major decline was noted in the incidence of AIDS dementia complex (ADC). Several factors point to a causal relationship. It is important now to review the evidence derived from clinical, cerebrospinal fluid (CSF) and neuropathological studies to determine whether the protective effect of zidovudine on the brain of patients with HIV infection has implications for clinical practice. It has been demonstrated in clinical studies that patients with ADC may improve with zidovudine treatment and that the development of ADC is rare in patients receiving the nucleoside analogue long term. In support of these clinical findings, CSF studies have revealed that the presence of HIV-1 p24 antigen has diagnostic value in patients with suspected ADC and that p24 antigen levels decline with zidovudine treatment. Supporting evidence has also come from neuropathological studies, which have demonstrated that zidovudine decreases HIV-specific neuropathological abnormalities. Recently, the Multicenter AIDS Cohort Study reported conflicting data which suggested that antiretroviral therapy is not protective against ADC; however, several methodological weaknesses of this study limit the general applicability of the findings and the conclusions. In view of the increasing body of evidence in support of the efficacy of zidovudine in the prevention and management of ADC in patients with HIV-1 infection, it seems reasonable to include this antiretroviral agent in any combination treatment regimen. Many questions remain to be answered, however, before management of such patients is optimised. Meanwhile, in order to increase both insight and evidence, it is imperative that ongoing and future clinical trials with antiretroviral drugs closely monitor all cases of progression to ADC.(ABSTRACT TRUNCATED AT 250 WORDS)
齐多夫定引入后,艾滋病痴呆综合征(ADC)的发病率显著下降。有几个因素表明存在因果关系。现在重要的是回顾来自临床、脑脊液(CSF)和神经病理学研究的证据,以确定齐多夫定对HIV感染患者大脑的保护作用是否对临床实践有影响。临床研究表明,ADC患者接受齐多夫定治疗可能会改善,并且长期接受核苷类似物治疗的患者很少发生ADC。支持这些临床发现的是,脑脊液研究显示,HIV-1 p24抗原的存在对疑似ADC患者具有诊断价值,并且p24抗原水平会随着齐多夫定治疗而下降。神经病理学研究也提供了支持证据,表明齐多夫定可减少HIV特异性神经病理学异常。最近,多中心艾滋病队列研究报告了相互矛盾的数据,表明抗逆转录病毒疗法对ADC没有保护作用;然而,这项研究的几个方法学弱点限制了这些发现和结论的普遍适用性。鉴于越来越多的证据支持齐多夫定在预防和管理HIV-1感染患者的ADC方面的疗效,将这种抗逆转录病毒药物纳入任何联合治疗方案似乎是合理的。然而,在优化此类患者的管理之前,仍有许多问题有待解答。同时,为了增加见解和证据,必须要求正在进行的和未来的抗逆转录病毒药物临床试验密切监测所有进展为ADC的病例。(摘要截选至250字)