Ragni M V, Amato D A, LoFaro M L, DeGruttola V, Van Der Horst C, Eyster M E, Kessler C M, Gjerset G F, Ho M, Parenti D M
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
Blood. 1995 May 1;85(9):2337-46.
To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1-infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.
为评估去羟肌苷（ddI）单药治疗以及齐多夫定（ZDV）与ddI的三种不同联合用药方案在无症状人类免疫缺陷病毒1型（HIV-1）感染中的安全性和疗效，我们对126例无症状HIV-1感染的血友病和非血友病受试者开展了一项开放标签的I/II期研究，这些受试者的CD4细胞计数为200至500/mm³，并根据既往齐多夫定治疗情况和基线CD4细胞计数进行分层。研究分组包括A组，低剂量联合用药（ZDV 150 mg和ddI 134 mg，每日）；B组，中等剂量联合用药（ZDV 300 mg和ddI 334 mg，每日）；C组，高剂量联合用药（ZDV 600 mg和ddI 500 mg，每日），以及D组，ddI单药治疗（ddI 500 mg，每日）。早期，血友病受试者出现肝毒性的频率更高（P = 0.008），但各治疗组之间的毒性无差异（P = 0.51），治疗所致临床终点的发生率也无差异（P = 0.41）。在最初12周内，A组和D组CD4细胞计数的中位数增幅较小，分别为44/mm³和42/mm³，低于B组和C组，分别为105/mm³和114/mm³（P = 0.015）。血友病状态（P = 0.0004）和既往ZDV治疗经历（P = 0.044）可独立预测治疗最初12周内较弱的CD4反应。使用回归模型并校正血友病状态、既往ZDV治疗情况和基线CD4后，所有治疗组在第12周时的病毒载量较基线均有显著下降（P = 0.0001），A组的中位数下降百分比（56.3%）显著低于B组、C组和D组（分别为94.6%、98.5%和91.9%，P = 。015）。尽管血友病受试者出现的肝毒性更大且CD4反应较弱，但去羟肌苷单药治疗以及与齐多夫定的联合治疗对无症状HIV-1感染患者是安全有效的。
