ACTG A5095

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究将比较三种非蛋白水解酶抑制剂(PI)治疗方案在HIV-1感染的初始治疗中的作用。治疗的目标将是抑制和维持HIV-1RNA水平&200拷贝/毫升。这项研究还将确定三种PI保留方案的安全性和耐受性。1.假设本研究将对三种主要的功效假设进行评估。假设I：HO：ABC/3TC/ZDV臂的病毒学失败率高于3TC/ZDV/EFV臂的病毒学失败率。H1：ABC/3TC/ZDV的病毒学失败率不低于3TC/ZDV/EFV臂的病毒学失败率。注意：这项试验不会评估ABC/3TC/ZDV与3TC/ZDV/EFV ARM相比是否存在较低的病毒学失败率。假设II：Ho：在ABC/3TC/ZDV/EFV和3TC/ZDV/EFV臂中，病毒学失败的时间分布没有差异。H1：在ABC/3TC/ZDV/EFV和3TC/ZDV/EFV臂中，病毒学失败的时间分布存在差异。假设III：Ho：在ABC/3TC/ZDV/EFV和ABC/3TC/ZDV臂中，病毒学失败的时间分布没有差异。H1：在ABC/3TC/ZDV/EFV和ABC/3TC/ZDV臂中，病毒学失败的时间分布存在差异。2.特殊目的A5095：本研究的主要目的是：1)比较三种初始PI节约型抗逆转录病毒方案抑制和维持HIV-1RNA和200拷贝/毫升(失败时间)的能力。2)确定三种初始PI保留方案的安全性和耐受性。A5097：这项研究的主要目标是：1)描述与EFV治疗和非EFV治疗相比，与EFV治疗相关的神经系统症状和体征的发生率、持续时间和认知运动效应。2)将这些发现与治疗最初24周内的EFV血清药物水平相关联。A5107：这项研究的主要目的是：1)描述25名HIV阳性受试者对BMS-232632的吸收和处置特征。2)研究BMS-232632在既往非含PI方案失败患者中的量效关系。3)探讨血浆BMS-232632药代动力学参数与胆红素变化的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will compare three protease inhibitor (PI) -sparing treatment options for the initial treatment of HIV-1 infection. The goal of therapy will be to suppress and maintain HIV-1 RNA levels < 200 copies/ml. This study would also determine the safety and tolerability of the three PI-sparing regimens. 1. Hypothesis Three primary efficacy hypotheses will be evaluated in this study. Hypothesis I: Ho: The rate of virologic failure in the ABC/3TC/ZDV arm is greater than the rate of virologic failure in the 3TC/ZDV/EFV arm. H1: The rate of virologic failure in the ABC/3TC/ZDV is not inferior to the rate of virologic failure in the 3TC/ZDV/EFV arm. NOTE: This trial will not evaluate whether there is a lower rate of virologic failure in the ABC/3TC/ZDV compared to the 3TC/ZDV/EFV arm. Hypothesis II: Ho:There is no difference in the distribution of time to virologic failure in the ABC/3TC/ZDV/EFV and the 3TC/ZDV/EFV arms. H1: There is a difference in the distribution of time to virologic failure in the ABC/3TC/ZDV/EFV and the 3TC/ZDV/EFV arms. Hypothesis III: Ho: here is no difference in the distribution of time to virologic failure in the ABC/3TC/ZDV/EFV and the ABC/3TC/ZDV arms. H1: There is a difference in the distribution of time to virologic failure in the ABC/3TC/ZDV/EFV and the ABC/3TC/ZDV arms. 2. Specific Aims A5095: The primary objectives of this study are to 1) to compare the ability of the three initial PI-sparing antiretroviral regimens to suppress and maintain HIV-1 RNA <200 copies/mL (time to failure). 2) To determine the safety and tolerability of the three initial PI-sparing regimens. A5097: The primary objectives of this study are to 1)To describe the incidence, duration, and cognitive motor effect of neurologic symptoms and signs associated with initiation of EFV therapy compared to therapy without EFV. 2) To correlate these findings with EFV serum drug levels over the initial 24 weeks of treatment. A5107: The primary objectives of this study are to 1) To describe the absorption and disposition characteristics of BMS-232632 in 25 HIV-positive subjects. 2) To investigate concentration-response relationships of BMS-232632 in patients who have previously failed non-PI-containing regimens. 3) To explore relationships between plasma BMS-232632 pharmacokinetic parameters and changes in bilirubin.