对齐多夫定不耐受或在使用齐多夫定后临床状况恶化的极晚期HIV感染患者进行的去羟肌苷剂量比较研究。德国去羟肌苷试验组。

A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group.

作者信息

Jablonowski H, Arasteh K, Staszewski S, Ruf B, Stellbrink H J, Schrappe M, Stoehr A, Haase W, Schomaker U, von Eisenhart Rothe B

机构信息

Department for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine University, Dusseldorf, Germany.

出版信息

AIDS. 1995 May;9(5):463-9.

PMID:7639971

Abstract

OBJECTIVE

Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddI; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated.

DESIGN

A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddI daily.

SETTING

The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres.

RESULTS

The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient).

CONCLUSIONS

This study cannot conclude on ddI efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddI therapy is considered, daily doses < 750 mg should be administered.

摘要

目的

齐多夫定（ZDV）是唯一已被证明可降低有症状HIV疾病患者死亡率的抗逆转录病毒药物，但其使用在很大一部分患者中受到不耐受的限制。此外，长期治疗后ZDV疗法的疗效似乎会下降，尤其是在HIV疾病晚期。因此，需要为患者提供替代抗逆转录病毒方案。在本研究中，对另一种HIV逆转录酶抑制剂去羟肌苷（ddI；2'，3'-双脱氧肌苷）进行了评估。

设计

共有426例对ZDV疗法不耐受或临床病情进展、CD4 +细胞计数≤150×10⁶/l的艾滋病或艾滋病相关综合征（ARC）患者被随机分为每日接受高剂量（体重≥60 kg者为750 mg，体重<60 kg者为500 mg）或低剂量（分别为200 mg和134 mg）的ddI治疗。

地点

患者从31个德国和奥地利艾滋病临床初级保健中心招募。

结果

在第二次中期分析后，由于胰腺炎发生率（9例对26例；相对风险，2.92；P = 0.003）和神经病变（28例对43例；相对风险，1.55；P = 0.05）在低剂量组更有利，差异有统计学意义，研究提前终止。低剂量组和高剂量组在6个月（80%对80%）和12个月（61%对65%）的生存率、死亡人数[82例（每100患者年43.6例）对84例（每100患者年44.4例）]、从ARC进展为艾滋病或死亡、或新的/复发性机会性感染的平均数量（每位患者2.8次对3次）方面均无差异。