ADEFOVIR DIPIVOXIL, INDINAVIR, ZIDOVUDINE, LAMIVUDINE IN VARIOUS DOSE

该方案描述了一项分层、随机、开放标签的研究，研究阿德福韦酯与茚地那韦联合齐多夫定和拉米夫定作为四联疗法，或与齐多夫定、拉米夫定或司他夫定三联疗法，治疗CD4细胞计数>或= 100/mm3， HIV-1 RNA基线拷贝数>或= 5000拷贝/mL的hiv感染患者，最长48周的安全性和有效性。本研究计划分两个阶段招募。在第一阶段，大约130名患者将按1:1:1:1:1的比例随机分配到五种治疗方案中的一种。患者将随机接受阿德福韦酯-茚地那韦-齐多夫定-拉米夫定或阿德福韦酯- indianvir和核苷抑制剂（随机分配接受齐多夫定、拉米夫定或他夫定）或接受茚地那韦、齐多夫定和拉米夫定三联治疗。此外，随机分配到含有阿德福韦地泊沃斯的一组的所有患者每日服用500毫克左旋肉碱。在第二阶段，额外的患者将以大约2:2:1的比例随机分配到三种治疗方案中的一种，样样量为100,100和50，分别在含有阿德福韦酯和茚那韦和拉米夫定的组，或齐多夫定和茚那韦和拉米夫定的组，或阿德福韦酯、茚那韦、齐多夫定和拉米夫定的组。与第一阶段一样，将给所有随机分配到含有阿德福韦酯组的患者每日服用500毫克左旋肉碱。治疗将持续48周。血浆HIV 1 RNA和CD4细胞计数将被测量以确定抗HIV活性。身体检查和实验室测试将用于监测患者的安全。在第20周时，血浆HIV-1 RNA浓度低于定量下限的患者将有资格继续总共48周的研究治疗。血浆HIV-1 RNA浓度未持续低于定量下限（在初始反应后）且至少14天后第二次血浆HIV-1 RNA浓度测定证实的患者将停药。此外，不能耐受任何指定的全剂量研究药物的患者也将在第24周访问时停药。

This protocol describes a stratified, randomized, open-label study of the safety and efficacy of adefovir dipivoxil with indinavir as quadruple therapy in combination with zidovudine and lamivudine or as triple combination administered with either zidovudine or lamivudine or stavudine for a maximum of 48 weeks in the treatment of HIV-infected patients with CD4 cell counts > or = 100/mm3 and a HIV-1 RNA baseline copy number > or =5,000 copies/mL. There are two phases of enrollment planned for this study. In phase I, approximately 130 patients will be randomized to one of five treatment regimens in a 1:1:1:1:1 ratio. Patients will be randomized to adefovir dipivoxil and indinavir and zidovudine and lamivudine or to adefovir dipivoxil and indianvir and a nucleoside inhibitor (randomly assigned to receive zidovudine, lamivudine or stavudine) or to triple combination therapy with indinavir, zidovudine and lamivudine. Additionally, a daily dose of L-carnitine 500 mg is administered to all patients randomized to an arm containing adefovir dipovoxil. In the second phase, additional patients will be randomized to one of three treatment regimens in approximately a 2:2:1 ratio to a sample size of 100, 100, and 50 in the arms containing adefovir dipivoxil and indinavir and lamivudine or to zidovudine and indinavir and lamivudine or to adefovir dipivoxil, indinavir, zidovudine and lamivudine, respectively. As in the first phase, a daily dose of L-carnitine 500 mg will be administered to all patients randomized to the arms containing adefovir dipivoxil. Treatment will be for an intended duration of 48 weeks. Plasma HIV 1 RNA and CD4 cell counts will be measured to determine anti-HIV activity. Physical examination and laboratory tests will be used to monitor patient safety. Patients with plasma HIV-1 RNA concentrations below the lower limit of quantification at week 20 will be eligible to continue on study treatment for a total of 48 weeks. Patients with plasma HIV-1 RNA concentrations that are not sustained below the lower limit of quantification (after an initial response) and confirmed by a second plasma HIV-1 RNA concentration drawn at least 14 days later will be discontinued. In addition, patients unable to tolerate any of the assigned study medication of full dose will also be discontinued at the week 24 visit.