HAART IN ACUTE/EARLY HIV INFECTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。具体目的：在对照临床试验的背景下，评估一段时间的益处？高活性抗逆转录病毒治疗（TL-HAART）在不同阶段急性感染/早期疾病（AIED）的有限疗程。在一个三的背景下？在一项为期一年的IV期随机临床试验中，我们将比较AIED诊断后两种不同的干预策略。具体来说，我们将以随机的方式检查，是否有一个？一年的HAART疗程为最近感染艾滋病毒的患者提供了持久的益处。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时间间隔，进一步研究这种益处是否仅限于这些个体的一部分。招募：所有诊断为AIED（即HIV持续时间< 12个月）的患者将有机会参与研究。在两年多的时间里，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，包括巴尔的摩的48名和加拿大的132名。入选标准：年龄？能够理解研究的目的（包括治疗AIED的具体理由），能够阅读、理解并签署知情同意书。除暴露后预防外无抗逆转录病毒治疗史；有能力吞下大量片剂/胶囊；在治疗开始前有生育潜力的妇女血清β - hcg呈阴性；在研究过程中愿意使用屏障避孕；排除标准；临床上有明显的医学状况，不能使用HAART；研究者认为，即使在初次出现时已怀孕，也不能充分遵守方案；在开始HAART治疗后两周内异常：血红蛋白<90 g/L；中性粒细胞计数< 1000 /mm3；血小板计数< 30,000/mm3， AST或ALT低于正常上限（ULN）的10倍；胰淀粉酶或脂肪酶> 3x ULN；无法根据基因型耐药试验结果设计研究治疗方案；血浆病毒载量< 5000拷贝/mL，除非可以确定感染发生在过去6个月内。随机化：随机化比例为1:1，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）分层。持续时间：第一年每个月对所有参与者进行随访，然后在接下来的两年每三个月进行一次。主要终点：治疗与未治疗患者首次就诊后24个月血浆病毒载量的比较。

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.