ACTG A5073:TWICE DAILY -V- ONCE DAILY HAARTAND SELF-ADMINISTERED VERSUS DOT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。虽然艾滋病毒和其他环境中的依从性研究侧重于患者相关因素和态度以及治疗相关因素的重要性，包括易于给药，给药频率，特别是药丸负担，作为依从性结果的关键因素，但尚未确定每日给药一次是否比两次增加依从性。事实上，目前尚不清楚每日一次给药是否比每日两次给药更可取，因为与可能更“宽容”的每日两次给药方案相比，每日一次给药错过给药的后果可能要大得多。另一方面，一旦每日给药，可能会允许广泛实施DOT以促进依从性，否则这一策略是不可行的，或者可能需要“修改”，以便只观察到两次每日剂量中的一次。然而，也有可能的是，对于监狱环境中的艾滋病毒和在有限时间内每周给予两次或三次结核病治疗的DOT的优势，在需要终身治疗的艾滋病毒感染中可能是暂时的，或者如果在机构环境之外进行无限期治疗，则可能被每日DOT的不便和负担所抵消。本研究将评估减少频率给药（每天两次vs一次，BID vs QD）和每天一次给药，24周直接观察（DOT- vs DOT+）有效的抗逆转录病毒治疗方案对病毒学抑制的程度和持久性的相对贡献。它还将检查24周的DOT训练对48周病毒学结果的可能性。额外的评估将评估两种给药方案和治疗策略的早期病毒学结果，以及这些结果预测48周内后续抗逆转录病毒疗效的能力。减少给药频率和DOT对生活质量和多种依从性指标（包括电子监测设备）的影响，以及安全性、耐受性和免疫反应，也将被评估。探索性分析将评估DOT的可行性，其成功与否可能取决于多中心AACTG试验中的多个因素。目标人群将是抗逆转录病毒感染者。建议研究的抗逆转录病毒药物，司他夫定缓释（d4T XR）（一种实验性d4T缓释制剂），恩曲他滨（FTC）（一种实验性核苷）和洛匹那韦/利托那韦（LPV/r）（一种许可的蛋白酶抑制剂），被选择是因为有利的药代动力学（例如，较长的细胞内或血浆半衰期），药丸负担，以及每日一次给药替代常规每日两次给药的潜力。目前这些药物的药物相互作用数据尚待确定或未知，尽管没有理论问题妨碍这些药物联合研究。这项研究假设，每天一次的强效抗逆转录病毒治疗方案可能能够通过允许不那么复杂的药物方案来改善艾滋病毒感染者的生活质量，而不会减轻病毒学抑制的程度和持久性。它还假设，在24周时，每天一次的DOT治疗方案比自我治疗方案更有可能导致病毒抑制。

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. While adherence studies in HIV and other settings have focused on the importance of patient-related factors and attitudes as well as treatment-related factors, including ease of administration, dosing frequency, and especially pill burden as key contributors to adherence outcomes, it has yet to be determined whether adherence increases with once, compared to twice, daily dosing. In fact, it is not clear whether once daily dosing is preferable to twice daily dosing since the consequences of a missed dose might be considerably greater in a once daily compared with a potentially more "forgiving" twice daily regimen. On the other hand, once daily dosing might allow widespread implementation of DOT to facilitate adherence, a strategy that would otherwise not be feasible, or might require "modification," such that only one of two daily doses is observed. It is also possible, however, that the advantages of DOT, clearly established for HIV in the prison setting and for tuberculosis treatment given twice or thrice weekly for a finite period, may be transient in HIV infection, which requires life-long treatment or may be offset by the inconvenience and burden of daily DOT if administered outside of an institutional setting for an indefinite treatment duration. This study will evaluate the relative contribution of reduced frequency dosing (twice versus once daily, BID versus QD) and for once-daily dosing, 24 weeks of direct observation (DOT- versus DOT+) of a potent antiretroviral regimen on the magnitude and durability of virologic suppression. It will also examine the possibility of a training effect of 24 weeks of DOT on virologic outcomes through week 48. Additional evaluations will assess early virologic outcomes in the two dosing schedules and treatment strategies and the ability of these outcomes to predict subsequent antiretroviral efficacy through week 48. The impact of reduced dosing frequency and DOT on quality of life and multiple adherence indicators, including electronic monitoring devices, will also be evaluated, together with safety, tolerance, and immunologic responses. Exploratory analyses will evaluate the feasibility of DOT, the success of which may rely on multiple factors, in a multicenter AACTG trial. The targeted population will be antiretroviral na¿ve. The antiretroviral agents proposed for study, stavudine extended release (d4T XR) (an investigational extended release formulation of d4T), emtricitabine (FTC) (an investigational nucleoside), and lopinavir/ritonavir (LPV/r) (a licensed protease inhibitor), were selected because of favorable pharmacokinetics (e.g., long intracellular or plasma half-life), pill burden, and the potential for once daily dosing as an alternative to conventional twice daily dosing. Drug-drug interaction data are pending or unknown at present for these agents, although there are no theoretical issues which would preclude study of these agents in combination. This study hypothesizes that once-daily treatments of a potent antiretroviral regimen may be able to improve the quality of life of persons with HIV by allowing less complicated drug regimens, without mitigating the magnitude and durability of virologic suppression. It also hypothesizes that DOT administration of a once-a-day regimen is more likely to result in viral suppression at 24 weeks than self administration of the same regimen.