ACTG A5073

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项随机、II期、三臂、开放标签研究，旨在比较每天两次和每天一次有效的抗逆转录病毒治疗，并比较自我给药治疗或在直接观察下实施的治疗。每名受试者将在这项研究中接受为期48周的跟踪调查。 这项研究将招募375名受试者：每个自我给药组150人，DOT组75人。该人群将由HIV感染者组成，他们是抗逆转录病毒天真的，血浆HIV-1RNA水平为2000拷贝/毫升。为了确保三种药物之间的平衡，受试者将根据筛查血浆HIV-1RNA水平进行分层：100,000拷贝/毫升和100,000拷贝/毫升。受试者将被随机分成三组中的一组：A组(Bid)、B组(Qd)或C组(Qd/DOT)。 这项研究的主要具体目的是比较一种有效的抗逆转录病毒方案在每天两次给药和一天一次给药时在48周内对艾滋病毒-1感染者实现持续病毒学应答的能力，比较一种有效的抗逆转录病毒方案在自我给药和直接观察下给药时在艾滋病毒-1感染者中通过24周实现持续病毒学应答的能力，并评估研究方案的安全性和耐受性。本研究的次要目的是通过探索在24周、48周以及随着时间的推移许多不同的复合病毒学和治疗终点定义的影响来评估治疗反应，以确定在第4周和第8周的抗逆转录病毒活性是否与整个48周的病毒学抑制相关，确定当与d4TXR和FTC一起服用时，BID和QD臂中的LPV/r谷浓度(Cmin)，以确定LPV/r Cmin是否与第4至48周的病毒学抑制相关，评估依从性与LPV/r Cmin之间的关系，以监测在接受QD治疗的受试者中LPV/r的意外积累，比较DOT组和非DOT组的LPV/r Cmin并确定非DOT组的LPV/r PK变异性是否更大，比较BID和QD研究方案中病毒学失败时受试者的病毒学耐药突变模式，比较BID和QD给药方案以及DOT和非DOT治疗方案之间的CD4+和CD8+T细胞应答，评估DOT方案的依从性及其对48周病毒学应答的影响，比较BID和QD给药方案以及DOT和非DOT治疗策略对生活质量参数和治疗依从性的影响探讨前24周的DOT治疗是否对生活质量和坚持24-48周的研究治疗有影响，评估受试者对DOT的态度(对于ARM C的受试者)，并探讨DOT策略在多中心AACTG试验中的可行性。

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 is a randomized, phase II, three arm, open-label study to compare twice daily and once daily potent antiretroviral therapy and to compare self-administered therapy or therapy administered under direct observation. Each subject will be followed on the study for 48 weeks. This study will enroll 375 subjects: 150 in each of the self-administered treatment arms, and 75 in the DOT arm. The population will consist of HIV-infected subjects who are antiretroviral naive, and who have plasma HIV-1 RNA levels 2000 copies/mL. To ensure balance among the three arms, subjects will be stratified based on screening plasma HIV-1 RNA levels: < 100,000 copies/mL and 100,000 copies/mL. Subjects will be randomized into one of three treatment arms: arm A (BID), arm B (QD), or arm C (QD/DOT). The primary specific aims of this study are to compare the ability of a potent antiretroviral regimen to achieve a sustained virologic response in HIV-1 infected subjects through week 48 when given twice daily and when given once daily, to compare the ability of a potent antiretroviral regimen to achieve a sustained virologic response in HIV-1 infected subjects through week 24 when self-administered and when administered under direct observation, and to evaluate the safety and tolerance of the study regimens. The secondary objectives of this study are to evaluate the treatment response by exploring the impact of a number of different composite virologic and treatment endpoint definitions at weeks 24, 48, and over time, to determine whether antiretroviral activity at weeks 4 and 8 correlates with virologic suppression through week 48, to determine LPV/r trough concentrations (Cmin) in the BID and QD arms, when given in conjunction with d4T XR and FTC, to determine if LPV/r Cmin correlates with virologic suppression at weeks 4 through 48, to evaluate the relationship between adherence and LPV/r Cmin, to monitor unexpected accumulation of LPV/r in subjects receiving QD treatment, to compare LPV/r Cmin in the DOT and non-DOT arms and to determine whether LPV/r PK variability is greater in the non-DOT arm, to compare the virologic resistance mutation profile patterns at the time of virologic failure among subjects in the BID and QD study regimens, to compare CD4+ and CD8+ T-cell responses between BID and QD dosing schedules and between DOT and non-DOT treatment strategies, to evaluate adherence to a DOT program and its impact on virologic response through week 48, to compare the impact of BID and QD dosing schedules and DOT and non-DOT treatment strategies on quality of life parameters and treatment adherence, to explore whether DOT treatment for the first 24 weeks has an effect on quality of life and adherence to study treatment between weeks 24 and 48, to evaluate subject attitude to DOT (for subjects in Arm C), and to explore the feasibility of DOT strategies in a multicenter AACTG trial.