ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM IN AIDS

描述（改编自申请人摘要）：对RFA的回应 AI-98-013，本申请是竞争性续期申请的一部分， 艾滋病临床试验组（ACTG） Beth Israel（BI）AIDS Clinical 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，并建议在新的赠款周期， 作为一个独立的单位。 基于15年的经验 在HIV相关临床研究方面的成就，BI的重点 调查人员包括ACTG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，并优化艾滋病毒感染妇女的护理， 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ACTG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，并探索 HIV-1感染的发病机制及其并发症，包括双 艾滋病毒和特定机会致病菌之间的定向关系。 BI站点还具有进一步实现 ACTG通过招募、入组和长期随访保留 处于HIV-1所有阶段的人口统计学上多样化的受试者人群 治疗HIV-1感染的I-IV期临床试验中的感染 及其相关并发症。 根据在抗逆转录病毒药物研究方面的丰富经验， 结核病（TB），并坚持结核病治疗，他们将开发新的 促进坚持高效抗逆转录病毒疗法的模式 并将评估多种药物的安全性/耐受性和抗病毒活性， 抗逆转录病毒联合疗法。 BI单位还建议验证 与RNA一起使用的免疫学“第三标记物”或另外的标记物 和CD 4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。 研究 HIV相关的并发症将集中在：（1）微生物和免疫 确定机会性感染风险和防护措施;（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的效果 恢复病原体特异性免疫功能;（5）蛋白酶的作用 HIV感染妇女中的抑制剂;和（6）感觉性多发性神经病， HIV相关的痴呆症，以及CNS中病毒感染的储库， 包括CSF抗逆转录病毒药代动力学。

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.