HAART IN ACUTE/EARLY HIV INFECTION

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 研究中心，而研究中心不一定是研究者所在的机构。 具体目标： ¿ 在对照临床试验的背景下，评估时间的益处？在艾滋病毒急性感染/早期疾病（AIED）的不同阶段接受有限疗程的高效抗逆转录病毒治疗（TL-HAART）。 在一个三的范围内？本研究为一项为期一年的IV期随机临床试验，我们将比较诊断为AIED后两种不同的干预策略。具体来说，我们将研究，在一个随机的方式，是否一个？一年的HAART疗程为最近感染HIV的患者提供了持久的益处。 如果是这样的话，我们将进一步研究这种益处是否仅限于这些个体的一个子集，基于暴露于HIV和开始治疗之间的时间间隔。 推荐： 所有诊断为AIED的患者（即，HIV持续时间< 12个月）将有机会参加研究。 在两年内，我们将招募180名患者进入该方案，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？18年 ¿ 能够理解研究目的（包括治疗AIED的具体依据），并能够阅读、理解和签署知情同意书。 ¿ 除暴露后预防外，无抗逆转录病毒治疗既往史 ¿ 吞咽大量片剂/胶囊的能力 ¿ 有生育能力的女性在开始治疗前血清β-HCG阴性 ¿ 研究期间愿意使用屏障避孕 排除标准 ¿ 排除使用HAART的具有临床意义的疾病 ¿ 研究者认为，任何可能妨碍充分依从方案（即使使用DOT）的疾病（如不受控制的药物滥用）的证据 ¿ 初次就诊时妊娠 ¿ HAART治疗开始后两周内停止：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倍正常值上限（ULN）;胰淀粉酶或脂肪酶> 3倍ULN;总胆红素> 3倍ULN ¿ 无法根据基因型耐药检测结果设计研究治疗方案 ¿ 血浆病毒载量<5，000拷贝/mL，除非可以最终确定感染发生在过去6个月内。 随机分组： 随机化比例为1：1，按急性感染（定义为过去2个月内感染）与早期感染（定义为过去2 - 12个月内感染）分层。 持续时间： 所有参与者将在第一年每月接受一次随访，然后在接下来的两年中每三个月接受一次随访。 终点： 主要终点： ¿ 所有治疗与未治疗患者首次出现后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.