ACTG A5202: EFAVIRENZ OR ATAZANAVIR WITH RITONAVIR IN ARV-NAIVE SUBJECTS (AIDS)

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IIIB期随机四臂研究，比较了开放标签利托那韦(RTV)增强型阿扎那韦(ATV)与依法韦伦(EFV)作为HIV-1感染的初始治疗药物联合每日恩曲他滨(FTC)/替诺福韦(TDF)或阿巴卡韦(ABC)/拉米夫定(3TC)以及部分盲用ABC/3TC与FTC/TDF联合RTV增强型ATV或EFV的有效性、安全性和耐受性。 假设：1)RTV增强型ATV联合FTC/TDF与EFV联合FTC/TDF具有同等的抗病毒效力。2)RTV增强型ATV联合ABC/3TC的抗病毒效果与EFV联合ABC/3TC相当。3)EFV联合ABC/3TC与EFV联合FTC/TDF的抗病毒效果相当。4)RTV增强型ATV联合ABC/3TC与RTV增强型ATV联合FTC/TDF的抗病毒效果相当。 主要目的：1)比较病毒学失败的两种方案的病毒学疗效，病毒学失败定义为16周或16周后血浆HIV-1RNA水平？1000拷贝/毫升与24周前或24周或24周后？200拷贝/毫升的时间。2)比较两种方案的安全性，安全性定义为首次发展为3级或体征、症状或实验室异常至少比基线高一级的时间。3)比较方案之间的耐受性和耐受性，耐受性定义为在初始治疗方案中改变一种或多种药物的时间。 这项研究将持续大约96周，超过最后一个科目的注册。将招募1800名受试者(每个治疗组450人)。受试者将HIV-1感染，抗逆转录病毒(ARV)药物-NAéve(在进入研究前的任何时间接受ARV治疗的天数)男性和女性-16岁，血浆HIV-1RNA水平和GT；1000拷贝/毫升。受试者将根据血浆HIV-1RNA水平100,000和100,000拷贝/毫升以及参加代谢性亚研究A5224的意图和资格进行分层筛选。 参赛的受试者将被随机分为以下一组： A组：EFV 600 mg，qd，FTC 200 mg/TDF，300 mg，qd，ABC/3TC，安慰剂，qd B组：EFV 600 mg，qd，ABC 600 mg/3TC，300 mg，qd，FTC/TDF，安慰剂qd C组：ATV 300 mg，每日1次，RTV 100 mg，每日1次，FTC 200 mg/TDF 300 mg，每日1次，ABC/3TC，安慰剂，每日1次 ARM D：ATV 300 mg qd+RTV 100 mg qd ABC 600 mg/3TC 300 mg qd FTC/TDF安慰剂qd 一项名为A5224的子研究将确定长期代谢影响：脂肪、血糖、骨密度和肾功能的变化。其主要目标如下：1)评估在含有ABC/3TC或FTC/TDF(B/D或A/C)的ARV方案开始后，治疗臂内外周脂肪变化(肢体脂肪)的变化。2)比较使用ABC/3TC和FTC/TDF两种ARV方案对腰椎和髋部的骨密度(BMD)的影响。子研究的假设是：1)A5202的FTC/TDF和ABC/3TC臂将与相对较少的肢体脂肪损失相关。2)与其他NRTI手臂相比，含有TDF的手臂将导致更高的骨丢失率。

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 phase IIIB, randomized, four-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced atazanavir (ATV) to efavirenz (EFV), in combination with either daily emtricitabine (FTC)/tenofovir (TDF) or abacavir (ABC)/lamivudine (3TC) and of partially blinded ABC/3TC compared to FTC/TDF in combination with either RTV-enhanced ATV or EFV as initial therapy for HIV-1 infection. Hypotheses: 1) RTV-enhanced ATV in combination with FTC/TDF is equivalent to EFV in combination with FTC/TDF with respect to antiviral potency. 2) RTV-enhanced ATV in combination with ABC/3TC is equivalent to EFV in combination with ABC/3TC with respect to antiviral potency. 3) EFV in combination with ABC/3TC is equivalent to EFV in combination with FTC/TDF with respect to antiviral potency. 4) RTV-enhanced ATV in combination with ABC/3TC is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to antiviral potency. Primary objectives: 1) 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. 2) To compare the safety between regimens with safety defined as the time to first development of Grade 3 or sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline. 3) To compare the tolerability between regimens with tolerability defined as the time to change in one or more drugs in the initial treatment regimen. The study will last approximately 96 weeks beyond the enrollment of the last subject. 1800 subjects (450 per treatment arm) will be enrolled. Subjects will be HIV-1-infected, antiretroviral (ARV) drug-na¿ve (days of ARV treatment at anytime prior to study entry) men and women ?16 years of age with plasma HIV-1 RNA levels >1000 copies/mL. Subjects will be stratified at screening based on plasma HIV-1 RNA levels <100,000 and ?100,000 copies/mL and intent and eligibility to enroll in the metabolic substudy A5224s. At entry subjects will be randomized to one of the following: ARM A: EFV 600 mg QD + FTC 200 mg/TDF 300 mg QD + ABC/3TC placebo QD ARM B: EFV 600 mg QD + ABC 600 mg/3TC 300 mg QD + FTC/TDF placebo QD ARM C: ATV 300 mg QD with RTV 100 mg QD + FTC 200 mg/TDF 300 mg QD + ABC/3TC placebo QD ARM D: ATV 300 mg QD with RTV 100 mg QD + ABC 600 mg/3TC 300 mg QD + FTC/TDF placebo QD A substudy, A5224, will determine long-term metabolic effects: changes in fat, blood sugar, bone density and renal function. Its primary objectives are as follows: 1) To assess changes within treatment arms in peripheral fat changes (limb fat) after the initiation of an ARV regimen containing ABC/3TC or FTC/TDF (Arms B/D or A/C). 2) To compare the effects of initiation of an ARV regimen containing ABC/3TC with those of a regimen containing FTC/TDF on bone mineral density (BMD), as assessed by lumbar spine and hip DEXA (Arms B/D versus A/C). The hypotheses of the substudy are 1) FTC/TDF and ABC/3TC arms in A5202 will be associated with relatively little loss of limb fat. 2) TDF-containing arms will lead to higher rates of bone loss when compared to the other NRTI arms.