HAART IN ACUTE/EARLY HIV INFECTION

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。 特定目标： ？在一项对照临床试验的背景下，评估在急性感染/艾滋病毒引起的早期疾病(AIED)的不同阶段进行限时高效抗逆转录病毒疗法(TL-HAART)的益处。 在为期三年的IV期随机临床试验的背景下，我们将比较两种不同的干预策略。具体地说，我们将以随机的方式检查HAART的一年疗程是否对最近感染艾滋病毒的患者提供持久的好处。如果是这样的话，我们将根据接触艾滋病毒和开始治疗之间的间隔，进一步检查这种益处是否仅限于此类个人的一部分。 招聘： 所有可以被诊断为艾滋病病毒感染(即持续12个月)的患者都将有机会参与这项研究。在两年的时间里，我们将招募180名患者加入该方案，其中包括大量的注射吸毒者，其中48人在巴尔的摩，132人在加拿大。 纳入标准 ？年龄？18岁 ？能够理解研究的目的(包括治疗AIED的具体理由)，并阅读、理解和签署知情同意文件。 ？除暴露后预防外，没有抗逆转录病毒治疗的病史 ？吞咽大量片剂/胶囊的能力 潜在育龄妇女治疗前血清β-HCG阴性 ·在研究过程中是否愿意使用屏障避孕 排除标准 ？临床上重要的医学状况将排除HAART的使用 ？调查员认为会妨碍充分遵守议定书的任何情况的证据(如不受控制的药物滥用)，即使是DOT ？初次分娩时怀孕 启动HAART后两周内异常：血红蛋白90 g/L；中性粒细胞计数1,000/mm~3；血小板计数30,000/mm~3，AST或ALT；10倍正常上限(ULN)；胰淀粉酶或脂肪酶；3倍ULN；总胆红素3倍ULN 无法根据基因耐药检测结果设计研究治疗方案 血浆病毒载量为5,000拷贝/毫升，除非可以确定感染发生在前6个月内。 随机化： 随机分组为1：1，并按急性感染(定义为最近2个月内的感染)和早期感染(定义为最近2-12个月内的感染)进行分层。 持续时间： 所有参与者在第一年每月跟踪一次，然后在接下来的两年每三个月跟踪一次。 终端： 主端点： ？比较所有接受治疗和未接受治疗的患者在首次发病24个月后的血浆病毒载量。

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. SPECIFIC AIM: ¿ Within the context of a controlled clinical trial, to evaluate the benefit of a time?limited course of Highly Active Antiretroviral Therapy (TL-HAART) at different stages of acute infection/early disease due to HIV (AIED). Within the context of a three?year phase IV randomized clinical trial, we will compare two different strategies for intervention following the diagnosis of AIED. Specifically, we will examine, in a randomized fashion, whether a one?year course of HAART provides lasting benefit in patients who have recently become infected with HIV. If this is the case, we will further examine whether the benefit is limited to a subset of such individuals, based on the interval between exposure to HIV and initiation of therapy. RECRUITMENT: All patients in whom a diagnosis of AIED (i.e., duration of HIV < 12 months) can be made will be offered the opportunity to participate in the study. Over two years, we will recruit 180 patients into the protocol, including significant numbers of IDUs, including 48 in Baltimore and 132 in Canadian sites. Inclusion Criteria ¿ Age ? 18 years ¿ Ability to understand the purpose of the study (including the specific rationale for the treatment of AIED) and to read, understand and sign the informed consent document. ¿ No prior history of antiretroviral therapy other than post-exposure prophylaxis ¿ Ability to swallow significant numbers of tablets/capsules ¿ Negative serum Beta-HCG in women of child-bearing potential prior to initiation of therapy ¿ Willingness to use barrier contraception during the course of the study Exclusion Criteria ¿ Clinically significant medical condition that would preclude the use of HAART ¿ Evidence of any condition (such as uncontrolled substance abuse) that would, in the opinion of the investigator, prevent adequate adherence to the protocol, even with DOT ¿ Pregnancy at the time of initial presentation ¿ Abnormalities within two weeks of initiating HAART: Hemoglobin <90 g/L; Neutrophil count < 1,000 /mm3; Platelet count < 30,000/mm3, AST or ALT > 10X upper limit of normal (ULN); Pancreatic amylase or lipase > 3x ULN; Total bilirubin > 3x ULN ¿ Inability to design a study treatment regimen based on the results of genotypic resistance testing ¿ Plasma viral load < 5,000 copies/mL, unless it can be conclusively established that infection occurred in the previous 6 months. Randomization: Randomization will be 1:1 and stratified by acute infection (defined as infection within the last 2 months) versus early infection (defined as infection within the last 2 - 12 months). Duration: All participants will be followed monthly for the first year, then every three months for the next two years. ENDPOINTS: Primary Endpoint: ¿ Comparison of the plasma viral load 24 months after initial presentation in all treated vs. untreated patients.