Interleukin 2 as Immune Therapy in Early HIV Infection

超出所提供的空间。这是一份修订后的申请，建议进行一项前瞻性随机试验，每日低剂量给药白介素2 （interleukin 2, 1L2）治疗早期HIV感染（即，在感染确定后不久，发现感染并使用高活性抗逆转录病毒疗法（HAART）治疗）。这项研究的长远目标是开发艾滋病毒感染的治疗方法，最大限度地减少对抗逆转录病毒药物慢性治疗的需求。在本应用中要验证的主要假设是，白介素2 （IL2）与高活性抗逆转录病毒疗法（HAART）结合使用，将使宿主免疫系统比单独使用HAART更有效地抑制HIV复制。作为急性感染和早期疾病研究项目（AIEDRP）的一部分，这一假设将通过每天皮下注射低剂量的il - 2来测试，这些受试者被诊断为HIV感染，接受HAART治疗，并在感染后一年内将血液中il - 2抑制到无法检测的水平（<50拷贝/ml）。该研究设计包含两个治疗周期，在每个治疗周期中，HAART将停止治疗长达12周，并测量所达到的病毒设定点。每个研究参与者将在一个治疗周期内接受il - 2。如果这个假设是正确的，在一个给定的治疗周期中，接受il - 2治疗的患者的病毒设定点应该比没有接受il - 2治疗的患者低。我们进一步假设HIV对HIV的抑制程度将与CD4+和CD8+ T细胞对复发性病毒血症的反应程度相关。为了验证这一假设，将用跨越所有HIV基因的HIV肽刺激短期淋巴细胞培养，并通过流式细胞术使用CD69和细胞内干扰素-的产生（作为细胞激活的指标）来测量被激活的细胞比例。获得的数据将有助于确定HIV的早期治疗是否在临床上有益，以及直接测量HIV反应细胞是否可以预测宿主免疫反应控制HIV复制的能力。该修订解决了对原始申请的所有批评，特别是将拟议的研究与先前使用lL2治疗早期HIV感染的研究区分开来。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. This is a revised application for a proposal to conduct a prospective, randomized trial of daily, low-dose administration of lnterleukin 2 (1L2) in the treatment of early HIV infection (i.e., infection that was identified, and treated with highly active antiretroviral therapy (HAART), soon after establishment of infection). The long-range of this research is to develop treatments for HIV infection that minimize the need for chronic therapy with antiretroviral medications. The major hypothesis to be tested in this application is that Interleukin 2 (IL2) given with highly active antiretroviral therapy (HAART) will enable the host immune system to suppress HIV replication more effectively than will HAART alone. This hypothesis will be tested by administering low doses of IL2 subcutaneously daily to a population of subjects whose HIV infection was diagnosed, treated with HAART, and suppressed to undetectable levels in the blood (<50 copies/ml) within one year of the time of infection as part of the Acute Infection and Early Disease Research Project (AIEDRP). The study design contains two treatment cycles, in each of which HAART will be stopped for up to 12 weeks and the viral set point that is achieved will be measured. Each study participant will receive IL2 during one of the treatment cycles. If the hypothesis is true, viral set points in a given treatment cycle should be lower in those who received IL2 in that cycle than in those who did not. We further hypothesize that the extent of HIV suppression of HIV will correlate with the magnitude of the CD4+ and CD8+ T cell responses to recurrent viremia. To test this hypothesis, short-term lymphocyte cultures will be stimulated with HIV peptides that span all HIV genes and the proportion of cells that are activated will be measured by flow cytometry using CD69 and intracellular production of interferon-,{ as indicators of cellular activation. The data obtained will help determine if early treatment of HIV is clinically beneficial, and whether direct measurement of HIV-reactive cells can predict the ability of the host immune response to control HIV replication. The revision addresses all points in the critique of the original application, in particular distinguishing the proposed research from previous research in the use of lL2 to treat early HIV infection. PERFORMANCE SITE ========================================Section End===========================================