Byers V S, Levin A S, Malvino A, Waites L, Robins R A, Baldwin R W
Immunology, Inc., San Francisco, California 94108.
AIDS Res Hum Retroviruses. 1994 Apr;10(4):413-20. doi: 10.1089/aid.1994.10.413.
Patients infected with HIV, including those with AIDS-related complex and AIDS, and failing treatment with antiretroviral agents such as zidovudine, have been evaluated following addition of trichosanthin to the antiretroviral agent regimen. This ribosomal inhibitory protein is specifically cytotoxic for HIV-infected macrophages and lymphocytes. Ninety-three patients were treated with trichosanthin, using a schedule of weekly, then monthly, intravenous injections of 1.2 mg of drug in combination with antiretroviral agents, usually zidovudine. Side effects included myalgias, fevers, mild elevation in liver function tests, and mild-moderate anaphylactic reactions, which respond well to therapy with steroids and/or benedryl. Reversible mental status changes were noted in two patients, both receiving concomitant therapy with ddI. Clinical responses to trichosanthin treatment were monitored primarily by changes in laboratory parameters, particularly levels of CD4+ T lymphocytes. In the total population evaluated for efficacy (85 patients) there was a significant increase in CD4+ cell levels after initiation of trichosanthin therapy. A second analysis performed on 72 patients measured the rate of change of CD4+ cells during therapy, using an "area under the curve" analysis. During therapy there was a median increase of 1.2 cells/mm3/month. In patients in the top 25th percentile, this increase was greater than 8.4 cells/mm3/month. In 59 of the 72 patients, responses could also be monitored by comparing the rate of loss of CD4+ cell levels on antiretroviral agents (zidovudine or ddI) alone, during the year prior to initiation of trichosanthin, to the rate of change when trichosanthin was added to the treatment regimen. During the period before trichosanthin treatment (311 +/- 11.7 days) the median loss of CD4+ cells was 6.91 cells/mm3/month. Addition of trichosanthin to the treatment regimen resulted in a median gain of 1.1 CD4+ cells/mm3/month.
对感染了人类免疫缺陷病毒（HIV）的患者，包括患有艾滋病相关综合征和艾滋病的患者，以及使用齐多夫定等抗逆转录病毒药物治疗失败的患者，在抗逆转录病毒药物治疗方案中添加天花粉蛋白后进行了评估。这种核糖体抑制蛋白对HIV感染的巨噬细胞和淋巴细胞具有特异性细胞毒性。93名患者接受了天花粉蛋白治疗，采用每周一次，然后每月一次静脉注射1.2毫克药物的方案，并与抗逆转录病毒药物联合使用，通常是齐多夫定。副作用包括肌痛、发热、肝功能检查轻度升高以及轻度至中度过敏反应，这些反应对类固醇和/或苯海拉明治疗反应良好。两名患者出现可逆的精神状态改变，两人均同时接受去羟肌苷治疗。主要通过实验室参数的变化，特别是CD4 + T淋巴细胞水平的变化来监测对天花粉蛋白治疗的临床反应。在评估疗效的总人群（85名患者）中，开始天花粉蛋白治疗后CD4 + 细胞水平显著增加。对72名患者进行的第二项分析使用“曲线下面积”分析来测量治疗期间CD4 + 细胞的变化率。治疗期间，CD4 + 细胞中位数每月增加1.2个细胞/mm³。在前25%的患者中，这种增加大于8.4个细胞/mm³/月。在72名患者中的59名患者中，也可以通过比较开始使用天花粉蛋白前一年单独使用抗逆转录病毒药物（齐多夫定或去羟肌苷）时CD4 + 细胞水平的下降率与添加天花粉蛋白到治疗方案后的变化率来监测反应。在天花粉蛋白治疗前的时期（311±11.7天），CD4 + 细胞的中位数损失为6.91个细胞/mm³/月。将天花粉蛋白添加到治疗方案中导致CD4 + 细胞中位数每月增加1.1个细胞/mm³。
