ANTIRETROVIRAL ACTIVITY OF HYDROXYUREA ALONE AND IN COMBINATION WITH DDI

该ACTG方案目的是在HIV血清阳性的情况下检查 患者，羟基脲的安全性和抗逆转录病毒活性 与单独使用DDI相比，DDI与DDI联合使用。主要假设 1)羟基脲在两种剂量下都是安全和耐受性良好的 将单独进行检查，并与DDI和2)一起进行检查 当使用双敌畏和羟基脲时，抗病毒效果会更好。 与作为单一疗法使用的任何一种相比，联合使用。这将是 是一项为期24周的I/II期随机、双盲、剂量范围研究 感染艾滋病毒的成年人，其CD4淋巴细胞计数在200-500之间。那里 将有两个为期12周的疗程和5个学习臂。药代动力学 将对所有受试者进行监测。用于定量的样本 HIV RNA水平、CD4/CD8淋巴细胞计数和dATP测量将是 在第2、4、8、12和24周获得。课程的最初12周部分 研究旨在收集数据，这些数据将用于执行 抗逆转录病毒活性分析。研究的五个分支是羟基脲 安慰剂每日1次加ddi 200 mg，每日2次，2)羟基尿素1000 mg，qd加ddi 安慰剂疗程4周，然后羟基尿素1000 mg，qd+DDI 200 mg，bid， 3)羟基脲1500 mg，qd加ddi安慰剂，每日2次，疗程4周，然后 羟基尿素1500 mg，qd加ddi 200 mg，2次/d，4)羟基尿素1000 mg，qd加 DDI 200 mg，2次/d；5)羟基尿素1500 mg，qd+DDI 200 mg，2次/d。这个 抗逆转录病毒活性分析中使用的主要比较将是 在羟基脲ddi联合治疗臂和ddi之间 单一疗法手臂。第八周的血浆HIV rna水平将用于 比较一下。在第12周结束后，关于组合的科目 治疗将继续使用他们目前的治疗方法；而受试者将继续使用DDI 单一疗法将继续使用ddi，并在指定的时间添加羟基脲。 剂量(1：1随机)，每日1000毫克或每日1500毫克。随机化 接受低剂量或高剂量羟基脲治疗的受试者 第12周的联合治疗将在研究开始时进行。 因此，所有受试者都将在12周内接受联合治疗。 至24岁，一半接受羟基尿素1000 mg，qd，另一半接受羟基尿素治疗 羟基尿素1500 mg，每日1次。在12到24周内，所有人 研究用药将是不含安慰剂的开放标签。这项研究是 正在进行的和治疗的武器仍然失明，因此研究结论和 其意义尚不能讨论。

The purpose of this ACTG protocol is to examine, in HIV-seropositive patients, the safety and antiretroviral activity of hydroxyurea alone and in combination with DDI compared with DDI alone. The primary hypotheses are 1) that hydroxyurea will be safe and well tolerated at the two doses that will be examined alone and in combination with ddI and 2) that there will be a more favorable antiviral effect when ddI and hyroxyurea are used in combination as compared to either one used as monotherapy. This will be a 24 week, phase I/II, randomized, double-blind, dose-ranging study in HIV-infected adults, whose CD4 lymphocyte count is between 200-500. There will be two 12-week treatment periods and 5 study arms. Pharmacokinetic monitoring will be performed on all subjects. Specimens for quantitative HIV RNA levels, CD4+/CD8+ lymphocyte counts, and dATP measurements will be obtained on weeks 2, 4, 8, 12 and 24. The initial 12-week portion of the study is designed to gather data that will be used to perform an antiretroviral activity analysis. The five study arms are 1) hydroxyurea placebo qd plus ddI 200 mg bid, 2) hydroxyurea 1000 mg qd plus ddI placebo bid for 4 weeks, then hydroxyurea 1000 mg qd plus ddI 200 mg bid, 3) hydroxyurea 1500 mg qd plus ddI placebo bid for 4 weeks, then hydroxyurea 1500 mg qd plus ddI 200 mg bid, 4) hydroxyurea 1000 mg qd plus ddI 200 mg bid, and 5) hydroxyurea 1500 mg qd plus ddI 200 mg bid. The principal comparison used in the antiretroviral activity analysis will be between the hydroxyurea + ddI combination therapy arms and the ddI monotherapy arm. The Week 8 plasma HIV RNA levels will be used in this comparison. After the completion of Week 12, subjects on combination therapy will remain on their current therapy; and subjects on ddI monotherapy will remain on ddI and have hydroxyurea added at an assigned dose (1:1 randomization) of 1000 mg qd or 1500 mg qd. Randomization of subjects in the ddI monotherapy arm to low or high dose hydroxyurea + ddI combination therapy at Week 12 will have occurred at study entry. Therefore, all subjects will receive combination therapy during Weeks 12 to 24, with half receiving hydroxyurea at a dose of 1000 mg qd and half receiving hydroxyurea at a dose of 1500 mg qd. During Weeks 12 to 24, all study medication will be open label with no placebos. The study is ongoing and treatment arms remain blinded, therefore study conclusions and significance can not yet be discussed.