Immunologic And Virologic Approaches To HIV-1 Therapeutics

作为一个艾滋病毒研究诊所，我们的重点仍然是解决以下问题的几个重要方面：如何最佳地使用和管理多类组合抗逆转录病毒疗法;如何在持续抗逆转录病毒疗法的框架内整合免疫疗法;如何确定启动抗逆转录病毒策略的最佳时间，以保护和重建免疫功能，同时最大限度地减少长期的长期抗逆转录病毒毒性，以及在使用和停用抗逆转录病毒药物的情况下，进行性HIV感染产生不良后果的一些预测因素。 在免疫调节实验室的临床研究部门（CRS），我们仍然致力于成功招募和完成“START”研究（抗逆转录病毒治疗的战略时机），旨在确定是否早期引入ART在以前未经治疗的患者转化为更好的临床结果。目前的卫生和人类服务部抗逆转录病毒指南建议对CD 4细胞计数为500个细胞/L或更低的HIV感染者开始HAART，但也强烈建议即使在CD 4细胞计数较高的患者中也考虑开始抗逆转录病毒治疗。然而，这些建议是有争议的，因为它们是基于大型观察性试验和专家意见的结果，而不是随机临床试验的数据。为了更严格和明确地解决这个问题，START试验是一项大型多国试验，招募了CD 4细胞计数高于500个细胞/L的抗逆转录病毒初治HIV感染者，并随机分配他们立即开始HAART或延迟HAART的开始，直到CD 4细胞计数福尔斯降至350个细胞/L以下。这项为期4-5年的试验的主要目的是比较两组由于进行性HIV感染或HAART本身毒性引起的不良后果（包括AIDS相关和非AIDS相关）的累积发生率。 通过这项试验和我们的其他艾滋病毒试验，我们还继续努力，通过外联活动，包括与当地诊所建立密切关系，为医疗服务不足的人群提供临床试验，以改善当地少数民族人口的机会。

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 enrollment and 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 definitely, the START trial is a large multi-national trial enrolling antiretroviral-naive HIV-infected individuals with CD4 cell counts above 500 cells/L and randomly assigning 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.