ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM IN AIDS

为了回应R.F.A. AI-98-013，此申请是艾滋病竞争性更新申请的一部分 临床试验组（ACTG）。Beth Israel（BI）AIDS ClinicalTrials Unit（ACTU）是ACTG的成员。 自1987年以来，该网络作为西奈山ACTU的一个子单位，并建议在新的赠款周期中建立一个 独立主机。基于15年的艾滋病相关临床研究经验和成果， BI研究者的关注点包括ACTG科学议程的几个最高优先级，包括 依从性、抗逆转录病毒毒性、代谢并发症，以及通过 了解性别对这些结果的影响。该提案旨在进一步实现《公约》的科学目标， ACTG研究议程委员会通过（1）促进设计和实施新的研究，将（a）： 为HIV-1感染及其并发症提供最佳治疗;和（B）：探索HIV-1感染的发病机制 及其并发症，包括艾滋病毒和特定机会病原体之间的双向关系。的BI 研究中心还具备通过（2）招募、登记和留住 长期随访I-IV期HIV-1感染所有阶段的人口统计学多样化受试者人群 治疗HIV-1感染及其相关并发症的临床试验。 基于抗逆转录病毒药物、结核病（TB）和TB依从性研究的丰富经验， 治疗，我们将开发新的模式，以促进坚持高活性抗逆转录病毒疗法（HAART），并将 评估多种药物抗逆转录病毒联合方案的安全性/耐受性和抗病毒活性。BI单位还 提出验证免疫学“第三标记物”或另外的标记物，与RNA和CD 4一起用作免疫学标记物。 在基于免疫的治疗干预的治疗试验中，作为临床和病毒学终点的复合替代物。 HIV相关并发症的研究将集中在：（1）确定机会性感染的微生物和免疫学指标 感染风险和保护;（2）代谢和营养并发症;（3）细胞因子作为疾病标志物的作用 （4）HAART对病原体特异性免疫功能恢复的影响; (5)蛋白酶促生长剂对HIV感染妇女的影响;（6）感觉性多发性神经病、HIV相关性痴呆，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。

In response to R.F.A. AI-98-013, this application is part of the competitive renewal application for the AIDS Clinical Trials Group (ACTG). The Beth Israel (BI) AIDS ClinicalTrials Unit (ACTU) has been a member of the ACTG network since 1987 as a subunitof the Mount Sinai ACTU, and proposes in the new grant cycle to be established as an independent main unit. Buildingon 15 years of experience and accomplishmentsin HIV-related clinical research, the focus of BI investigators encompasses several of the highest prioritiesof the ACTG scientific agenda, including adherence, antiretroviral toxicities, metabolic complications, and optimizingthe care of HIV-infected women throughan understanding of the influence of gender on these outcomes. This proposal aims to further the scientific goals of the ACTG research agenda committees by (1) contributing to the design and implementation of novel studies that will (a): provide optimal therapy for HIV-1 infection and its complications; and (b): explore the pathogenesis of HIV-1 infection and its complications, including bidirectional relationships between HIV and specific opportunisticpathogens. The BI site also has the demonstrated capability to further the goals of the ACTG by (2) recruiting, enrolling,and retainingin long term follow up a demographically diverse populationof 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, we will develop novel models to promote adherence to highly active antiretroviraltherapy (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 therapeuticinterventions. Studies of HIV-related complications will focus on: (1) microbial and immunologic measures that defineopportunistic infection risk and protection; (2) metabolic and nutritionalcomplications; (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 inhibitorsin HIV-infected women; and (6) sensory polyneuropathy, HIV-associated dementia,and reservoirs of viral infection tn the CNS, including CSF antiretroviralpharmacokinetics.