Harris M, Deutsch G, MacLean J D, Tsoukas C M
McGill University AIDS Centre, Montreal, Quebec, Canada.
AIDS. 1994 Aug;8(8):1109-13. doi: 10.1097/00002030-199408000-00011.
The intestinal parasite Cryptosporidium is a common cause of chronic diarrhoea in AIDS patients and is responsible for significant morbidity and mortality. No effective treatment is currently available for this condition. Here we aim to determine the safety, tolerance, and clinical effect of letrazuril in the treatment of AIDS-related Cryptosporidiosis.
A prospective, open-label study of letrazuril was performed.
The study was conducted at the Immune Deficiency Treatment Centre (IDTC) of Montreal General Hospital, a tertiary-care centre with inpatient and outpatient facilities.
All HIV-positive patients presenting to the IDTC between November 1991 and January 1993 who had symptomatic intestinal Cryptosporidiosis were enrolled in this protocol. Sixteen participants entered the study and 15 were available for evaluation, having completed at least 2 weeks on the study medication.
Patients received letrazuril daily in escalating doses of 50 to 100 mg orally for 6 weeks. Clinical and laboratory evaluations were performed weekly during the treatment phase, with a follow-up evaluation 4 weeks after the end of this phase, for a total study period of 10 weeks.
Response to letrazuril was assessed by eradication of Cryptosporidial oocysts from the stool and symptomatic improvement in diarrhoea and abdominal pain. Haematological, biochemical, and electrocardiographic parameters were also studied to evaluate potential toxicities of the treatment.
Fourteen evaluable patients had baseline CD4 lymphocyte counts ranging from 3 to 99 x 10(6)/l cells (mean, 30 x 10(6)/l cells). (The fifteenth evaluable patient had a CD4 count 235 x 10(6)/l.) Of these 14 patients, five showed a major response (symptomatic improvement and eradication of Cryptosporidial oocysts from the stool), two had a minor response (symptomatic improvement with persistence of oocysts in stool), and seven had no response to therapy with letrazuril. Seven patients developed a transient drug-related rash.
Fifty per cent of the AIDS patients in this study experienced an improvement in their Cryptosporidial disease while receiving letrazuril. No serious dose-related toxicities were observed. Larger Phase II trials are needed to evaluate the safety and efficacy of letrazuril in AIDS-associated intestinal Cryptosporidiosis.
肠道寄生虫隐孢子虫是艾滋病患者慢性腹泻的常见病因，可导致显著的发病率和死亡率。目前对此病症尚无有效的治疗方法。我们旨在确定来曲唑在治疗艾滋病相关隐孢子虫病中的安全性、耐受性及临床效果。
对来曲唑进行了一项前瞻性、开放标签研究。
研究在蒙特利尔综合医院免疫缺陷治疗中心进行，该中心是一家具备住院和门诊设施的三级医疗中心。
所有在1991年11月至1993年1月期间前往免疫缺陷治疗中心就诊、患有症状性肠道隐孢子虫病的HIV阳性患者均纳入本方案。16名参与者进入研究，15名完成了至少2周的研究药物治疗，可供评估。
患者每日口服来曲唑，剂量从50毫克递增至100毫克，持续6周。治疗阶段每周进行临床和实验室评估，该阶段结束后4周进行随访评估，总研究期为10周。
通过粪便中隐孢子虫卵囊的清除以及腹泻和腹痛症状的改善来评估对来曲唑的反应。还研究了血液学、生化和心电图参数，以评估治疗的潜在毒性。
14名可评估患者的基线CD4淋巴细胞计数范围为3至99×10⁶/升细胞（平均为30×10⁶/升细胞）。（第15名可评估患者的CD4计数为235×10⁶/升。）在这14名患者中，5名有主要反应（症状改善且粪便中隐孢子虫卵囊清除），2名有轻微反应（症状改善但粪便中仍有卵囊），7名对来曲唑治疗无反应。7名患者出现了短暂的药物相关皮疹。
本研究中50%的艾滋病患者在接受来曲唑治疗时隐孢子虫病病情有所改善。未观察到严重的剂量相关毒性。需要进行更大规模的II期试验来评估来曲唑在艾滋病相关肠道隐孢子虫病中的安全性和有效性。
