ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM IN AIDS

描述(改编自申请人的摘要)：回应RFA AI-98-013，此申请是竞争续签申请的一部分 艾滋病临床试验小组(ACTG)。贝丝以色列(BI)艾滋病诊所 审判股(ACTU)自1987年以来一直是ACTG网络的成员 西奈山ACTU的子单位，并提议在新的赠款周期中 作为一个独立的主体单位成立。以15年的经验为基础 和HLV相关临床研究的成就，BI的重点 调查人员涵盖了委员会的几个最高优先事项 科学议程，包括依从性、抗逆转录病毒毒性、代谢 并发症，并通过一种 了解性别对这些结果的影响。这项建议 旨在通过以下方式促进委员会研究议程委员会的科学目标 有助于设计和实施新的研究， 为HIV-I感染及其并发症提供最佳治疗方法，并探索 HIV-1感染及其并发症的发病机制，包括胆汁淤积症 艾滋病毒与特定的机会性病原体之间的定向关系。 BI网站还具有证明的能力，以促进 通过招募、登记和保留长期跟踪的ACTG 艾滋病毒-1所有阶段受试者的人口统计多样性 治疗HIV-1感染的I-IV期临床试验中的感染 及其相关的并发症。 基于抗逆转录病毒药物研究的丰富经验， 结核病(TB)，并坚持结核病治疗，他们将开发出新的 促进坚持高效抗逆转录病毒治疗(HAART)的模型 并将评估一种多药的安全性/耐受性和抗病毒活性 抗逆转录病毒联合疗法。商业智能部门还提议验证一个 免疫“第三标记物”或与RNA一起使用的附加标记物 和CD4，作为临床和病毒学终点的复合替代物 基于免疫的治疗干预的治疗试验。的研究 与HLV相关的并发症将集中在：(1)微生物和免疫学 确定机会性感染风险和保护的措施；(2) 代谢和营养并发症；(3)细胞因子作为标志物的作用 疾病进展和抗逆转录病毒药物疗效；(4)HAART的作用 病原菌特异性免疫功能的恢复；(5)蛋白酶的作用 艾滋病毒感染妇女中的抑制剂；以及(6)感觉性多发性神经病， 艾滋病毒相关性痴呆症，以及中枢神经系统中的病毒感染宿主， 包括脑脊液抗逆转录病毒药物动力学。

DESCRIPTION (adapted from the applicant's abstract): In response to RFA AI-98-013, this application is part of the competitive renewal application for the AIDS Clinical Trials Group (ACTG). The Beth Israel (BI) AIDS Clinical Trials Unit (ACTU) has been a member of the ACTG network since 1987 as a subunit of the Mount Sinai ACTU, and proposes in the new grant cycle to be established as an independent main unit. Building on 15 years of experience and accomplishments in HlV-related clinical research, the focus of BI investigators encompasses several of the highest priorities of the ACTG scientific agenda, including adherence, antiretroviral toxicities, metabolic complications, and optimizing the care of HlV-infected women through an understanding of the influence of gender on these outcomes. This proposal aims to further the scientific goals of the ACTG research agenda committees by contributing to the design and implementation of novel studies that will provide optimal therapy for HIV-I infection and its complications, and explore the pathogenesis of HIV-1 infection and its complications, including bi- directional relationships between HIV and specific opportunistic pathogens. The BI site also has the demonstrated capability to further the goals of the ACTG by recruiting, enrolling, and retaining in long term follow up a demographically diverse population of subjects at all stages of HIV-1 infection in Phase I-IV clinical trials for the treatment of HIV-1 infection and its related complications. Based on extensive experience with the study of antiretroviral agents, tuberculosis (TB), and adherence to TB treatment, they will develop novel models to promote adherence to highly active antiretroviral therapy (HAART) and will assess the safety/tolerance and antiviral activity of a multi-drug antiretroviral combination regimen. The BI unit also proposes to validate an immunologic "third marker" or additional markers for use, together with RNA and CD4, as a composite surrogate for clinical and virologic endpoints in treatment trials of immune-based therapeutic interventions. Studies of HlV-related complications will focus on: (1) microbial and immunologic measures that define opportunistic infection risk and protection; (2) metabolic and nutritional complications; (3) the role of cytokines as markers of disease progression and antiretroviral drug efficacy; (4) effects of HAART on restoration of pathogen-specific immune functions; (5) effects of protease inhibitors in HIV-infected women; and (6) sensory polyneuropathy, HIV-associated dementia, and reservoirs of viral infection in the CNS, including CSF antiretroviral pharmacokinetics.