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的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 这是一项IIIB期、随机、四组研究，比较了开放标签利托那韦（RTV）增强阿扎那韦（ATV）与依法韦仑（EFV）的疗效、安全性和耐受性，与每日恩曲他滨（FTC）/替诺福韦（TDF）或阿巴卡韦（ABC）/拉米夫定（3 TC）联合治疗，以及部分盲法ABC/3 TC与FTC/TDF联合RTV增强的ATV或EFV作为HIV初始治疗相比，1例感染。 假设：1）就抗病毒效力而言，RTV增强的ATV联合FTC/TDF与EFV联合FTC/TDF相当。2)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。 3)EFV联合ABC/3 TC的抗病毒效力等同于EFV联合FTC/TDF。 4)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。 主要目标：1）比较病毒学失败（定义为确认血浆HIV-1 RNA水平的时间）方案之间的病毒学疗效？16周或之后至24周之前1000拷贝/mL，或？第24周或之后> 200拷贝/mL。 2)比较治疗方案之间的安全性，安全性定义为至首次发生3级或体征、症状或实验室异常的时间，该异常至少比基线时高1级。 3)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。 研究将在最后一例受试者入组后持续约96周。将入组1800例受试者（每个治疗组450例）。 受试者将是HIV-1感染、抗逆转录病毒（ARV）药物初治（入组研究前任何时间接受ARV治疗的天数）的男性和女性？16岁，血浆HIV-1 RNA水平>1000拷贝/mL。 受试者将在筛选时根据血浆HIV-1 RNA水平<100，000和？100，000拷贝/mL，并且有意愿和资格入组代谢子研究A5224 s。 入组时，受试者将被随机分配至以下任一组： A组：EFV 600 mg QD + FTC 200 mg/TDF 300 mg QD + ABC/3 TC安慰剂QD B组：EFV 600 mg QD + ABC 600 mg/3 TC 300 mg QD + FTC/TDF安慰剂QD C组：ATV 300 mg QD + RTV 100 mg QD + FTC 200 mg/TDF 300 mg QD + ABC/3 TC安慰剂QD D组：ATV 300 mg QD + RTV 100 mg QD + ABC 600 mg/3 TC 300 mg QD + FTC/TDF安慰剂QD 一项子研究A5224将确定长期代谢效应：脂肪、血糖、骨密度和肾功能的变化。 其主要目的如下：1）评估开始含ABC/3 TC或FTC/TDF的ARV方案（B/D或A/C组）后治疗组内外周脂肪变化（肢体脂肪）的变化。 2)通过腰椎和髋关节DEXA评估，比较含ABC/3 TC的ARV方案与含FTC/TDF的ARV方案对骨密度（BMD）的影响（B/D组vs A/C组）。 该子研究的假设是1）A5202中的FTC/TDF和ABC/3 TC组将与相对较少的肢体脂肪损失相关。 2)与其他NRTI组相比，含TDF组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.