ACTG A5202

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 中心，不一定是研究者的机构。 目前的HIV-1感染初步治疗指南为患者和提供者提供了一些选择（可在http：//www.aidsinfo.nih.gov/上查阅）。 已经有越来越多的批准的抗逆转录病毒药物和研究表明，当采用有效的，耐受性良好的，简单的方案时，病毒学的成功率很高。 在卫生与公众服务部（DHHS）的首选方案中，两种核苷逆转录酶抑制剂（NRTI）与NNRTI EFV的联合用药是最简单的，并且在迄今为止进行的随机对照试验中具有最高的总体成功率[1-3]。 然而，新的药物最近已被批准，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组合与延长的半衰期，可能提供独特的优势，超过既定的治疗。 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性，随后剩余的治疗方案。 本研究将比较RTV增强的ATV与EFV联合每日FTC/TDF或ABC/3 TC，以及ABC/3 TC与FTC/TDF联合EFV或RTV增强的ATV作为HIV-1感染的初始治疗。 假设 就抗病毒效力而言，RTV增强的ATV与FTC/TDF组合等同于EFV与FTC/TDF组合。 就抗病毒效力而言，RTV增强的ATV与ABC/3 TC组合等同于EFV与ABC/3 TC组合。 EFV联合ABC/3 TC的抗病毒效力等同于EFV联合FTC/TDF。 就抗病毒效力而言，与ABC/3 TC组合的RTV增强的ATV等同于与FTC/TDF组合的RTV增强的ATV。 主要目的遵循以下模式：比较研究PI（RTV增强的ATV）与研究NNRTI（EFV）的每种NRTI组合;以及当与研究PI或研究NNRTI联合使用时，NRTI组合相互比较。 针对三个主要目标（有效性、安全性和耐受性）中的每一个进行这四项比较。 比较病毒学失败方案之间的病毒学疗效，病毒学失败定义为至确认的血浆HIV-1 RNA水平在16周或之后和24周之前≥ 1000拷贝/mL或在24周或之后≥ 200拷贝/mL的时间。 比较治疗方案之间的安全性，安全性定义为至首次出现3级或4级体征、症状或实验室检查异常的时间，至少比基线时高1级。 比较治疗方案之间的耐受性，耐受性定义为初始治疗方案中一种或多种药物发生变化的时间。

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.