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

ACTG A5202：依非韦伦或阿扎那韦联合利托那韦治疗未感染抗逆转录病毒药物的受试者（艾滋病）

• 批准号: 7605754
• 负责人: JUDITH Ann ABERG
• 金额: $ 33.8万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605754
• 关键词: AIDS clinical trial group; Acquired Immunodeficiency Syndrome; Age-Years; Anti-Retroviral Agents; Antiviral Agents; Atazanavir; Blinded; Blood Glucose; Bone Density; Computer Retrieval of Information on Scientific Projects Database; DEXA; Daily; Development; Eligibility Determination; Enrollment; Failure; Fatty acid glycerol esters; Funding; Grant; HIV-1; Hip region structure; Infection; Institution; Label; Laboratories; Lamivudine; Lead; Limb structure; Metabolic; Peripheral; Pharmaceutical Preparations; Phase; Placebos; Plasma; RNA; Randomized; Rate; Renal function; Research; Research Personnel; Resources; Ritonavir; Safety; Screening procedure; Signs and Symptoms; Source; Tenofovir; Time; Treatment Protocols; United States National Institutes of Health; Upper arm; Vertebral column; Week; Woman; abacavir; base; bone loss; day; efavirenz; emtricitabine; men

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.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 这是一项IIIB期，随机，四臂研究，比较开放标签的利托纳维尔（RTV）增强的atazanavir（ATV）与Efavirenz（EFV）的效率，安全性和耐受性，并与每日的Emtricitabine（FTC）/Tenofovir（FTC）/tenofovir（abcine of Abc）（abc）（abc）（abc）（abc）（abc）（abc）（abc）（EFV）（EFV）（EFV）（abc）与FTC/TDF与RTV增强的ATV或EFV相比，盲目的ABC/3TC作为HIV-1感染的初始疗法。 假设：1）与FTC/TDF结合使用RTV增强的ATV等效于EFV与FTC/TDF相对于抗病毒效能的结合。 2）与ABC/3TC联合使用RTV增强的ATV等于EFV与ABC/3TC相对于抗病毒效力的结合。 3）EFV与ABC/3TC结合使用，相当于EFV与FTC/TDF相对于抗病毒效力的结合。 4）与ABC/3TC结合使用RTV增强的ATV等效于RTV增强的ATV与FTC/TDF相对于抗病毒效能而言。 主要目标：1）比较具有病毒学衰竭方案之间的病毒学效率，定义为确认的等离子HIV-1 RNA水平的时间？1000份在16周或24周之前，24周之前，或在24周或24周或之后进行200份/ml。基线。 3）将方案之间的耐受性与最初治疗方案中一种或多种药物变化的耐受性进行比较。 这项研究将持续约96周，超出上一个学科的入学人数。将招募1800名受试者（每个治疗组450名）。受试者将是HIV-1感染的，抗逆转录病毒（ARV）药物（在研究进入之前的任何时间进行ARV治疗的天数）男性和女性？16岁的血浆HIV-1 RNA水平> 1000份/mL。受试者将根据血浆HIV-1 RNA水平<100,000和？100,000份/ml进行筛查，并有资格参加代谢质量A5224S。 入境对象将被随机分为以下一个： ARM A：EFV 600 mg QD + FTC 200 mg/tdf 300 mg QD + ABC/3TC安慰剂QD 手臂B：EFV 600 mg QD + ABC 600 mg/3tc 300 mg QD + FTC/TDF安慰剂QD ARM C：ATV 300 mg QD，带RTV 100 mg QD + FTC 200 mg/tdf 300 mg QD + ABC/3TC安慰剂QD 手臂D：ATV 300 mg QD，带RTV 100 mg QD + ABC 600 mg/3tc 300 mg QD + FTC/TDF安慰剂QD A5224的物质将确定长期代谢作用：脂肪，血糖，骨密度和肾功能的变化。它的主要目标如下：1）评估含有ABC/3TC或FTC/TDF（臂B/D或A/C）的ARV方案的主动性后，外周脂肪变化（肢体脂肪）的变化。 2）将含有ABC/3TC的ARV方案的倡议与含有FTC/TDF方案的倡议的影响对骨矿物质密度（BMD）的影响，如腰椎和HIP DEXA（ARMS B/D与A/C）所评估。该物质的假设为1）A5202中的FTC/TDF和ABC/3TC臂将与肢体脂肪的损失相对较小。 2）与其他NRTI臂相比，含TDF的手臂将导致更高的骨质流失率。