Simpson D M, Katzenstein D A, Hughes M D, Hammer S M, Williamson D L, Jiang Q, Pi J T
Mount Sinai Medical Center, New York, New York 10029, USA.
AIDS. 1998 Dec 24;12(18):2425-32. doi: 10.1097/00002030-199818000-00011.
To determine the frequency of peripheral neuropathy and myopathy in HIV-infected subjects enrolled in a combination antiretroviral treatment trial.
AIDS Clinical Trial Group (ACTG) protocol 175 was a multicenter, double-blind, placebo-controlled, clinical trial. A total of 2467 subjects were randomized to one of four single or combination regimens, containing zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), and their respective placebos. Site investigators reported peripheral neuropathy, and the diagnosis of distal symmetrical neuropathy (DSP) was established by the study authors. Myalgia, muscle weakness and creatine phosphokinase (CPK) were prospectively assessed in a subset of the antiretroviral-naive cohort (n = 1067).
Of 222 site diagnoses of neuropathy, 109 (49%) were DSP. There was a significant difference between treatment arms for rate of DSP and time to first grade 2 or higher DSP (ZDV-ddC, 6%; ZDV, 4%; ZDV-ddl, 4%; ddl, 3%; P = 0.029). Age and Karnofsky score were significant predictors of DSP. Fifty-six (54%) out of 104 patients with DSP remained on study medication at full (n = 29) or reduced (n = 27) dose within 6 months of developing neuropathy. There was no significant difference between treatment arms in the rate of myalgia or muscle weakness. The median CPK of subjects on ZDV-ddC was significantly higher than other study treatments, although CPK levels did not correlate with symptoms of myopathy. Only six subjects were diagnosed with myopathy during the study (one ZDV-ddl, one ZDV-ddC, and four ddl).
DSP and myopathy may occur with current dosing regimens of combination antiretroviral therapy, and should be diagnosed using stringent criteria. ZDV-ddC was associated with the highest rate of DSP, although features of myopathy were not significantly different between treatment regimens.
确定参加联合抗逆转录病毒治疗试验的HIV感染受试者中周围神经病变和肌病的发生率。
艾滋病临床试验组（ACTG）方案175是一项多中心、双盲、安慰剂对照的临床试验。共有2467名受试者被随机分配到四种单一或联合治疗方案之一，这些方案包含齐多夫定（ZDV）、去羟肌苷（ddI）、扎西他滨（ddC）及其各自的安慰剂。各研究点的研究者报告周围神经病变情况，远端对称性神经病变（DSP）的诊断由研究作者确定。对初治抗逆转录病毒治疗队列中的一个亚组（n = 1067）前瞻性评估肌痛、肌肉无力和肌酸磷酸激酶（CPK）。
在222例由研究点诊断为神经病变的病例中，109例（49%）为DSP。各治疗组之间DSP发生率及出现2级或更高级别DSP的时间存在显著差异（ZDV-ddC组为6%；ZDV组为4%；ZDV-ddI组为4%；ddI组为3%；P = 0.029）。年龄和卡诺夫斯基评分是DSP的显著预测因素。104例DSP患者中有56例（54%）在出现神经病变后6个月内继续以全量（n = 29）或减量（n = 27）服用研究药物。各治疗组之间肌痛或肌肉无力的发生率无显著差异。ZDV-ddC组受试者的CPK中位数显著高于其他研究治疗组，尽管CPK水平与肌病症状无关。在研究期间仅6例受试者被诊断为肌病（1例ZDV-ddI组、1例ZDV-ddC组和4例ddI组）。
联合抗逆转录病毒治疗的当前给药方案可能会发生DSP和肌病，应使用严格标准进行诊断。ZDV-ddC组的DSP发生率最高，尽管各治疗方案之间肌病特征无显著差异。
