Immunologic And Virologic Approaches To HIV-1 Therapeutics

HIV-1 治疗的免疫学和病毒学方法

基本信息

批准号：
8946344
负责人：
Richard Davey
金额：
$ 51.47万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8946344
关键词：
Acquired Immunodeficiency Syndrome Acute Address Anti-Retroviral Agents CD4 Lymphocyte Count Chronic Clinic Clinical Clinical Research Clinical Trials Complex Data Development Enrollment Expert Opinion Goals Guidelines HIV HIV Infections HIV-1 Highly Active Antiretroviral Therapy Immune Immunologics Improve Access Incidence Individual Infection Integration Host Factors Investigation L Cells Laboratories Minority Outcome Patients Pharmaceutical Preparations Population Predictive Factor Randomized Randomized Clinical Trials Recommendation Research Staging Therapeutic Time Toxic effect Translating Underserved Population United States Dept. of Health and Human Services adverse outcome alternative treatment antiretroviral therapy arm base falls immune function immunoregulation insight mortality outreach reconstitution tool treatment strategy

项目摘要

Our focus as an HIV research clinic continues to address several important aspects of the following questions: how to optimally use and administer multi-class combination anti-retroviral therapy; how to integrate immune based therapies within a framework of ongoing antiretroviral therapy; how to determine the optimal time for initiation of antiretroviral strategy in order to preserve and reconstitute immune function while at the same time minimizing long-term antiretroviral toxicities, and what are some of the predictive factors for the development of adverse consequences of progressive HIV infection both on and off antiretroviral medications. In the Clinical Research Section (CRS) of the Laboratory of Immunoregulation we remain dedicated to the successful completion of the "START" study (Strategic Timing of AntiRetroviral Treatment) aimed at determining whether early introduction of ART in previously-untreated patients translates into better clinical outcomes. Current Department of Health and Human Services Antiretroviral Guidelines recommend the initiation of HAART for HIV-infected individuals with CD4 cell counts of 500 cells/L or less, but also strongly recommend consideration of initiating antiretroviral treatment even in those with higher CD4 cell counts. However, these recommendations are controversial in that they are based upon the outcomes of large observational trials and expert opinion rather than on data from a randomized clinical trial. In order to address this question more rigorously and definitively and remove the bias of expert opinion, the START trial is a large multi-national trial that has enrolled antiretroviral-naive HIV-infected individuals with CD4 cell counts above 500 cells/L and randomly assigned them either to begin HAART immediately or to delay the start of HAART until the CD4 cell count falls below 350 cells/L. The primary goal of this 4-5 year trial is to compare the two arms in terms of the cumulative incidence of adverse consequences (both AIDS-related and non-AIDS related) ascribable either to progressive HIV infection or to the toxicities of HAART itself. With this and with our other HIV trials we also continue our efforts to improve access to clinical trials by local minority populations through an outreach that includes a close relationship with local clinics for medically under-served populations.

我们作为HIV研究诊所的重点继续解决以下问题的几个重要方面：如何最佳地使用和管理多级组合抗逆转录病毒疗法；如何在持续的抗逆转录病毒疗法的框架内整合基于免疫的疗法；如何确定抗逆转录病毒策略的最佳时间，以保持和重建免疫功能，同时最大程度地减少长期抗逆转录病毒毒性，以及哪些预测因素导致进行进展HIV感染的不良后果以及抗抗病毒药物的不良后果。在免疫调节实验室的临床研究部分（CRS）中，我们仍然致力于成功完成“开始”研究（抗逆转录病毒治疗的战略时机），旨在确定是否在以前未经治疗的患者中早期引入ART是否会转化为更好的临床结果。当前的卫生和公共服务部抗逆转录病毒指南建议启动HAART针对500细胞/L或更少的CD4细胞计数的HIV感染者，但也强烈建议您即使在CD4较高细胞计数的患者中开始启动抗逆转录病毒治疗。但是，这些建议是有争议的，因为它们是基于大型观察试验和专家意见的结果，而不是基于随机临床试验的数据。为了更严格，更明确地解决这个问题，消除了专家意见的偏见，开始试验是一项大型跨国试验，它已招募了具有CD4细胞计数超过500个细胞/L的抗逆性HIV感染的抗逆转录病毒的HIV感染者，并随机分配了它们以立即开始HAART或延迟CD4 Cell Cult Count fall the CD4 Cell Cunts falls falls 350 plow 350 cell 350 lafs/l。这项为期4 - 5年试验的主要目标是根据与渐进艾滋病毒感染或HAART本身的毒性相关的不良后果（与AIDS相关和非AID相关的不利后果（与AIDS相关和非AID相关）的累积发生率相比。借助这一问题，我们还继续努力通过包括与当地诊所的密切关系来改善当地少数民族人群的临床试验的机会，以提供医疗服务不足的人群。