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，旨在进行一项前瞻性随机试验，研究每日低剂量给予白细胞介素2（1 L2）治疗早期HIV感染（即，感染被确定，并在感染建立后不久用高效抗逆转录病毒疗法（HAART）治疗）。这项研究的长期目标是开发艾滋病毒感染的治疗方法，最大限度地减少抗逆转录病毒药物慢性治疗的需要。在本申请中待检验的主要假设是，与高效抗逆转录病毒疗法（HAART）一起给予白细胞介素2（IL 2）将使宿主免疫系统比单独HAART更有效地抑制HIV复制。将通过每天皮下给予低剂量的IL 2对受试者群体进行测试，作为急性感染和早期疾病研究项目（AIEDRP）的一部分，所述受试者群体的HIV感染被诊断，用HAART治疗，并在感染时间的一年内被抑制至血液中不可检测的水平（<50拷贝/ml）。研究设计包含两个治疗周期，每个周期将停止HAART长达12周，并测量达到的病毒设定点。每名研究参与者将在一个治疗周期期间接受IL 2。如果假设是真的，在给定的治疗周期中，在该周期中接受IL 2的患者的病毒设定点应低于未接受IL 2的患者。我们进一步假设，HIV抑制HIV的程度将与CD 4+和CD 8 + T细胞对复发性病毒血症的反应程度相关。为了检验这一假设，将用跨越所有HIV基因的HIV肽刺激短期淋巴细胞培养物，并且将通过流式细胞术使用CD 69和细胞内产生的干扰素α作为细胞活化的指标来测量活化的细胞的比例。所获得的数据将有助于确定早期治疗HIV是否具有临床益处，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批评中的所有问题，特别是将拟议的研究与先前使用IL 2治疗早期HIV感染的研究区分开来。性能现场=

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===========================================