Immunologic And Virologic Approaches To HIV-1 Therapeutics

作为艾滋病毒研究诊所，我们的重点继续解决以下问题的几个重要方面：如何以最佳方式使用和管理多类联合抗逆转录病毒治疗；如何在进行中的抗逆转录病毒治疗的框架内整合基于免疫的治疗；如何确定启动抗逆转录病毒策略的最佳时间，以保存和重建免疫功能，同时最大限度地减少长期抗逆转录病毒毒副作用，以及在服用和停用抗逆转录病毒药物的情况下，进行性艾滋病毒感染不良后果发展的一些预测因素。 在免疫调节实验室的临床研究科(CRS)，我们仍然致力于成功完成“START”研究(抗逆转录病毒治疗的战略时机)，该研究旨在确定在以前未接受治疗的患者中及早引入ART是否会转化为更好的临床结果。美国卫生与公众服务部目前的抗逆转录病毒指南建议对CD_4细胞数为500个/L或以下的艾滋病毒感染者开始进行HAART，但也强烈建议考虑开始抗逆转录病毒治疗，即使是CD_4细胞数较高的人。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的结果和专家意见，而不是基于随机临床试验的数据。为了更严格和明确地解决这个问题，并消除专家意见的偏见，START试验是一项大型的多国试验，招募了CD_4细胞数超过500个/L的抗逆转录病毒初治艾滋病毒感染者，并随机分配他们要么立即开始HAART，要么推迟开始HAART，直到CD_4细胞数降至350个/L以下。这项为期4-5年的试验的主要目标是比较这两种药物在可归因于HIV进行性感染或HAART本身毒性的不良后果(艾滋病相关和非艾滋病相关)的累积发生率。在进行这项和我们的其他艾滋病毒试验的同时，我们还继续努力通过外联活动改善当地少数群体获得临床试验的机会，其中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服务。

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.