ACTG A5202

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。目前的HIV-1感染初始治疗指南为患者和提供者提供了许多选择（可在http://www.aidsinfo.nih.gov/上获得）。越来越多的获批抗逆转录病毒药物和研究表明，当采用有效、耐受性良好和简单的方案时，在病毒学上取得了很高的成功。在美国卫生与公众服务部（DHHS）的首选方案中，两种核苷类逆转录酶抑制剂（nrti）与NNRTI EFV是最简单的组合，并且在迄今为止所做的随机对照试验中具有最高的总体成功率[1-3]。然而，新的药物最近被批准提供简单的每日一次的蛋白酶抑制剂（pi）以及每日一次的NRTI组合，其半衰期延长，可能比现有的治疗方法提供独特的优势。随着新型药物的出现，评估它们在优化HIV-1管理中的作用至关重要。这包括了解相对效力、耐受性、出现的耐药模式，以及如果新方案出现耐药，随后剩下的治疗方案。本研究将比较rtv增强型ATV与EFV联合每日FTC/TDF或ABC/3TC的使用情况，以及ABC/3TC与FTC/TDF联合EFV或rtv增强型ATV作为HIV-1感染初始治疗的比较。rtv增强ATV与FTC/TDF联合使用的抗病毒效力与EFV与FTC/TDF联合使用的抗病毒效力相当。rtv增强型ATV联合ABC/3TC的抗病毒效力与EFV联合ABC/3TC相当。就抗病毒效力而言，EFV与ABC/3TC联合使用与EFV与FTC/TDF联合使用等效。就抗病毒效力而言，rtv增强型ATV与ABC/3TC联合与rtv增强型ATV与FTC/TDF联合等效。主要目标是比较研究PI （RTV-enhanced ATV）和研究NNRTI （EFV）对每种NRTI组合的影响；当与研究PI或研究NNRTI一起使用时，NRTI相互组合。这四项比较分别针对三个主要目标（疗效、安全性和耐受性）。比较病毒学失败的方案之间的病毒学疗效，病毒学失败的定义是在16周或之后和24周之前确认血浆HIV-1 RNA水平>=1000拷贝/mL或在24周或之后>=200拷贝/mL。比较两种方案的安全性，安全性定义为首次出现3级或4级体征、症状或实验室异常的时间，且至少比基线高一级。比较不同治疗方案之间的耐受性，耐受性定义为在初始治疗方案中更换一种或多种药物的时间。

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. Current guidelines for the initial treatment of HIV-1 infection provide a number of options for patients and providers (available at http://www.aidsinfo.nih.gov/). There have been an ever-growing number of approved ARV agents and studies that demonstrate high levels of virologic success when employing potent, well-tolerated, and simple regimens. Of the Department of Health and Human Services (DHHS) preferred regimens, two nucleoside reverse transcriptase inhibitors (NRTIs) with the NNRTI EFV is the simplest combination to take and has had the highest overall success rates in randomized controlled trials done to date [1-3]. However, novel agents have recently been approved that provide simple once daily protease inhibitors (PIs) as well as once daily NRTI combinations with prolonged half-lives that may offer unique advantages over established therapies. As novel agents become available it is critical to assess their role in optimizing the management of HIV-1. This includes understanding the relative potency, tolerability, resistance patterns that emerge, and the consequent remaining treatment options if drug resistance occurs for newer regimens. This study will compare the use of RTV-enhanced ATV to EFV, in combination with either daily FTC/TDF or ABC/3TC, and of ABC/3TC compared to FTC/TDF in combination with either EFV or RTV-enhanced ATV as initial therapy for HIV-1 infection. Hypotheses ¿¿¿ RTV-enhanced ATV in combination with FTC/TDF is equivalent to EFV in combination with FTC/TDF with respect to antiviral potency. ¿¿¿ RTV-enhanced ATV in combination with ABC/3TC is equivalent to EFV in combination with ABC/3TC with respect to antiviral potency. ¿¿¿ EFV in combination with ABC/3TC is equivalent to EFV in combination with FTC/TDF with respect to antiviral potency. ¿¿¿ RTV-enhanced ATV in combination with ABC/3TC is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to antiviral potency. The primary objectives follow a pattern of comparing the study PI (RTV-enhanced ATV) with the study NNRTI (EFV) for each of the NRTI combinations; and the NRTI combinations with each other, when used with the study PI or the study NNRTI. These four comparisons are made for each of the three main objectives (efficacy, safety, and tolerability). ¿¿¿ To compare virologic efficacy between regimens with virologic failure defined as the time to confirmed plasma HIV-1 RNA level >=1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after week 24. ¿¿¿ To compare the safety between regimens with safety defined as the time to first development of Grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline. ¿¿¿ To compare the tolerability between regimens with tolerability defined as the time to change in one or more drugs in the initial treatment regimen.