Montaner J S, Gill J, Singer J, Raboud J, Arseneau R, McLean B D, Schechter M T, Ruedy J
Canadian HIV Trials Network, St. Paul's Hospital/University of British Columbia, Vancouver, Canada.
J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jun 1;12(2):153-7. doi: 10.1097/00042560-199606010-00008.
We assessed the safety and surrogate markers' effect of acemannan as an adjunctive to antiretroviral therapy among patients with advanced HIV disease receiving zidovudine (ZDV) or didanosine (ddI) in a randomized, double-blind, placebo-controlled trial of acemannan (400 mg orally four times daily). Eligible patients of either sex had CD4 counts of 50-300/microl twice within 1 month of study entry and had received 26 months of antiretroviral treatment (ZDV or ddI) at a stable dose for the month before entry. CD4 counts were made every 4 weeks for 48 weeks. P24 antigen was measured at entry and every 12 weeks thereafter. Sequential quantitative lymphocyte cultures for HIV and ZDV pharmacokinetics were performed in a subset of patients. Sixty-three patients were randomized. All were males (mean age 39 years). The mean baseline CD4 counts were 165 and 147/microl in the placebo and acemannan groups, respectively; 90 percent of the patients were receiving ZDV at entry. Six patients in the acemannan group and five in the placebo group developed AIDS-defining illnesses. There was no statistically significant difference between the groups at 48 weeks with regard to the absolute change or rate of decline at CD4 count. Among ZDV-treated patients, the median rates of CD4 change (ACD4) in the initial 16 weeks were - 121 and - 120 cells per year in the placebo and acemannan groups, respectively ( p = 0.45), ACD4 from week 16 to 48 was 0 and - 61 cells per year in the acemannan and placebo groups (p = .11), respectively. There was no statistical difference between groups with regard to adverse events, p24 antigen, quantitative virology, or pharmacokinetics. Twenty-four patients, 11 receiving placebo and 13 receiving acemannan, discontinued study therapy prematurely, none due to serious adverse reactions. Our results demonstrate that acemannan at an oral daily dose of 1600 mg does not prevent the decline in CD4 count characteristic of progressive HIV disease. Acemannan showed no significant effect on p24 antigen and quantitative virology. Acemannan was well tolerated and showed no significant pharmacokinetic interaction with ZDV.
在一项随机、双盲、安慰剂对照试验中，我们评估了乙酰甘露聚糖作为抗逆转录病毒疗法辅助药物，对接受齐多夫定（ZDV）或去羟肌苷（ddI）治疗的晚期HIV疾病患者的安全性及替代标志物的影响。试验中，乙酰甘露聚糖的服用方式为口服，每日4次，每次400mg。符合条件的患者为男性或女性，在研究入组1个月内CD4细胞计数两次为50 - 300/微升，且在入组前1个月以稳定剂量接受了26个月的抗逆转录病毒治疗（ZDV或ddI）。在48周内，每4周进行一次CD4细胞计数。入组时及此后每12周检测一次p24抗原。对部分患者进行了HIV和ZDV药代动力学的连续定量淋巴细胞培养。63名患者被随机分组。所有患者均为男性（平均年龄39岁）。安慰剂组和乙酰甘露聚糖组的平均基线CD4细胞计数分别为165/微升和147/微升；90%的患者入组时接受ZDV治疗。乙酰甘露聚糖组有6名患者、安慰剂组有5名患者出现了艾滋病相关疾病。在48周时，两组在CD4细胞计数的绝对变化或下降速率方面无统计学显著差异。在接受ZDV治疗的患者中，安慰剂组和乙酰甘露聚糖组在最初16周内CD4细胞变化中位数速率（ACD4）分别为每年 - 121个细胞和 - 120个细胞（p = 0.45），在第16周至48周期间，乙酰甘露聚糖组和安慰剂组的ACD4分别为每年0个细胞和 - 61个细胞（p = 0.11）。在不良事件、p24抗原、定量病毒学或药代动力学方面，两组之间无统计学差异。24名患者提前终止了研究治疗，其中11名接受安慰剂，13名接受乙酰甘露聚糖，均非因严重不良反应。我们的结果表明，每日口服剂量为1600mg的乙酰甘露聚糖不能预防进展性HIV疾病特征性的CD4细胞计数下降。乙酰甘露聚糖对p24抗原和定量病毒学无显著影响。乙酰甘露聚糖耐受性良好，与ZDV无显著药代动力学相互作用。
