ACTG A5073

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一项随机、II期、三组、开放标签研究，旨在比较每日两次和每日一次强效抗逆转录病毒治疗，并比较自我给药治疗或直接观察下给药治疗。每例受试者将在研究期间接受48周随访。本研究将入组375例受试者：每个自我给药治疗组150例，DOT组75例。人群将包括未接受过抗逆转录病毒治疗且血浆HIV-1 RNA水平2000拷贝/mL的HIV感染受试者。为了确保三组之间的平衡，将根据筛选血浆HIV-1 RNA水平对受试者进行分层：<100，000拷贝/mL和100，000拷贝/mL。受试者将被随机分配至三个治疗组之一：A组（BID）、B组（QD）或C组（QD/DOT）。 本研究的主要具体目的是比较强效抗逆转录病毒治疗方案在HIV-1感染受试者中每日两次和每日一次给药直至第48周实现持续病毒学应答的能力，比较强效抗逆转录病毒治疗方案在HIV-1感染受试者中达到持续病毒学应答的能力，给药时和直接观察下给药时，并评价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第24周、第48周和一段时间内许多不同的复合病毒学和治疗终点定义的影响来评价治疗应答，以确定第4周和第8周的抗逆转录病毒活性是否与第48周的病毒学抑制相关，以确定BID和QD组的LPV/r谷浓度（Cmin），当与d4 T XR和FTC联合给药时，确定LPV/r Cmin是否与第4周至第48周的病毒学抑制相关，评价依从性与LPV/r Cmin之间的关系，监测接受QD治疗的受试者中LPV/r的非预期蓄积，比较DOT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研究方案中受试者在病毒学失败时的病毒学耐药突变谱模式，比较BID和QD给药方案之间以及DOT和非DOT治疗策略之间的CD 4+和CD 8 + T细胞应答，评价对DOT方案的依从性及其对第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，探索前24周的DOT治疗是否对生活质量和第24 - 48周期间对研究治疗的依从性有影响，评估受试者对DOT的态度（C组受试者），并探索多中心AACTG试验中DOT策略的可行性。

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.