Vella S, Floridia M, Dally L G, Tomino C, Fragola V, Weimer L E, Milazzo F, Mazzotta F, Moroni M, Pastore G, Scalise G, Sinicco A, Ortona L, De Rienzo B, Dianzani F
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Aug 15;12(5):462-9. doi: 10.1097/00042560-199608150-00004.
Although the efficacy of switching from zidovudine (AZT) to didanosine (ddI) has already been evaluated in controlled studies, prior investigations were not specifically designed to evaluate this issue in patients with acquired immune deficiency syndrome (AIDS). This open, randomized, multicenter study (ISS 901) was designed to evaluate the clinical benefit in patients with AIDS of switching to ddI after 6-18 months of AZT and no major intolerance. Patients were randomized to continue AZT, maintaining the current dosage at randomization (n = 79), or to receive ddI (n = 80) at the dosage of 375 mg and 250 mg b.i.d. for body weight > 60 and < or = 60 kg, respectively. Primary efficacy measures were survival and time to new AIDS-defining events, analyzed by the intent-to-treat approach. The two groups were comparable for baseline characteristics, follow-up (15 months), and time spent on allocated treatment. At the end of the study, 104 patients (48 AZT, 56 ddI) had died and 90 had at least one new AIDS-defining event (44 AZT, 46 ddI). Kaplan-Meier estimates of survival and of time to first new AIDS-defining event showed no differences between the treatment groups. No differences were detected in other efficacy measurements (p24 antigenemia, CD4+ count, Karnofsky score, and body weight), occurrence of severe toxicities, and treatment modifications. Pancreatitis occurred only in ddI-treated patients (6%). In our population of patients with advanced disease, switching from AZT to ddI did not produce apparent benefits, suggesting that application of this strategy earlier in the course of human immunodeficiency virus disease should be considered.
尽管在对照研究中已经评估了从齐多夫定（AZT）转换为去羟肌苷（ddI）的疗效，但先前的研究并非专门设计用于评估获得性免疫缺陷综合征（AIDS）患者的这一问题。这项开放性、随机、多中心研究（ISS 901）旨在评估在接受AZT治疗6 - 18个月且无严重不耐受情况后转换为ddI对AIDS患者的临床益处。患者被随机分为继续使用AZT组，随机维持当前剂量（n = 79），或接受ddI组（n = 80），体重> 60 kg者剂量为375 mg，体重≤ 60 kg者剂量为250 mg，每日两次。主要疗效指标为生存率和出现新的AIDS定义事件的时间，采用意向性分析方法进行分析。两组在基线特征、随访时间（15个月）以及接受分配治疗的时间方面具有可比性。研究结束时，104例患者（48例AZT组，56例ddI组）死亡，90例患者至少出现了一项新的AIDS定义事件（44例AZT组，46例ddI组）。Kaplan-Meier生存估计和首次出现新的AIDS定义事件的时间在治疗组之间未显示出差异。在其他疗效测量指标（p24抗原血症、CD4 + 细胞计数、卡诺夫斯基评分和体重）、严重毒性的发生情况以及治疗调整方面也未检测到差异。胰腺炎仅发生在接受ddI治疗的患者中（6%）。在我们的晚期疾病患者群体中，从AZT转换为ddI并未产生明显益处，这表明应考虑在人类免疫缺陷病毒疾病病程早期应用这一策略。
