Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study.
Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study.
复制标题
人类免疫缺陷病毒 (HIV) 感染中循环 p24 抗原水平和对双脱氧胞苷的反应。
DOI：
10.7326/0003-4819-110-3-189
复制
发表时间：
1989
影响因子：
39.2
通讯作者：
Herbert H. Schaumburg
中科院分区：
文献类型：
--
作者：
T. Merigan;G. Skowron;S. Bozzette;Richman Dd;R. Uttamchandani;M. Fischl;R. Schooley;M. Hirsch;W. Soo;C. Pettinelli;Herbert H. Schaumburg
研究目的
确定双脱氧胞苷在获得性免疫缺陷综合征（AIDS）或晚期AIDS相关综合征患者中的安全性和有效性。
设计
一项部分随机化的I期和II期门诊、剂量范围探索研究。
设置
四所大学医学中心涉及政府支持的艾滋病临床试验转诊单位。
患者
61例AIDS或晚期AIDS相关复合体患者，血清p24抗原滴度≥ 100 pg/mL。
干预措施
根据耐受性和获益，每4小时口服0.06、0.03、0.01或0.005 mg/kg体重的双脱氧胞苷，持续3至6个月。
测量值和主要结果
在接受0.06和0.03 mg/kg的患者中，在治疗的前几周发生了弥漫性皮疹、发热和口疮性口炎，但随后消退。造血抑制是罕见的。接受0.06 mg/kg和0.03 mg/kg的患者发生外周感觉神经病变，并在停药后改善。大多数患者的血清p24抗原较基线值显著下降（P <0.01）。在0.03 mg/kg剂量下，CD 4淋巴细胞一过性升高。在0.005 mg/kg剂量下，皮疹、发烧和阿弗他口腔炎轻微或不存在。在接受0.01 mg/kg的所有患者中发生的周围神经病变的严重程度低于接受更高剂量的患者。在0.005 mg/kg剂量下，偶尔观察到周围神经病变。在接受0.01 mg/kg剂量的大多数艾滋病相关综合征患者中观察到血清p24抗原的显著抑制，而在接受0.005 mg/kg剂量的患者中较少见。
结论
毒性较小的双脱氧胞苷方案值得临床评估晚期抗人类免疫缺陷病毒-1（HIV）感染。一些研究交替双脱氧胞苷和齐多夫定正在进行中。
STUDY OBJECTIVE
To determine the safety and efficacy of dideoxycytidine in patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex.
DESIGN
A partially randomized phase I and II outpatient, dose-ranging study.
SETTING
Four university medical centers involving government-supported referral AIDS Clinical Trial Units.
PATIENTS
Sixty-one patients with AIDS or advanced AIDS-related complex and 100 pg/mL or more serum p24 antigen titers.
INTERVENTIONS
Dideoxycytidine was administered orally at 0.06, 0.03, 0.01, or 0.005 mg/kg body weight every 4 hours for 3 to 6 months depending on tolerance and benefit.
MEASUREMENTS AND MAIN RESULTS
In patients receiving 0.06 and 0.03 mg/kg, diffuse erythematous rash, fever, and aphthous stomatitis occurred in the first weeks of therapy, but resolved later. Hematopoietic suppression was rare. Peripheral sensory neuropathy occurred in patients receiving 0.06 mg/kg and 0.03 mg/kg and improved after discontinuation of therapy. Serum p24 antigen fell significantly (P less than 0.01) from baseline entry values in most of these patients. The CD4 lymphocytes rose transiently at the 0.03 mg/kg dosage. At the 0.005 mg/kg dosage, skin rash, fever, and aphthous stomatitis were mild or absent. Peripheral neuropathy, which occurred in all patients receiving 0.01 mg/kg was less severe than at higher dosages. At the 0.005 mg/kg dosage, peripheral neuropathy was occasionally seen. Significant suppression of serum p24 antigen was seen in most patients with AIDS-related complex receiving 0.01 mg/kg and less frequently in patients receiving 0.005 mg/kg.
CONCLUSIONS
Less toxic regimens of dideoxycytidine merit clinical assessment for advanced anti-human immunodeficiency virus-1 (HIV) infection. Several studies alternating dideoxycytidine and zidovudine are in progress.