IV OR SQRHIL2 IN HIV INFECTED SUBJECTS ON HAART

本ACTG方案的目的是评价 间歇性静脉注射重组人白细胞介素2（rhIL-2）或 在HIV感染受试者中皮下给药高活性 抗逆转录病毒治疗（HAART）与单独HAART相比。 主 假设包括：1）在不同 rhIL-2的间歇给药途径（IV vs.皮下 与高活性抗逆转录病毒方案相比， 单独使用高效抗逆转录病毒疗法的比例 CD 4计数较随机化前增加50%的受试者 rhIL-2治疗一年后的基线值和CD 4+细胞的变化率 计数; 2）安全性，公差， 以及这些方案对生活质量的影响，以及3） 免疫细胞表型和功能以及艾滋病毒的可测量变化 当HAART治疗时， 与单独HAART相比，在rhIL-2的情况下使用。 ACTG 872 子研究的次要假设是， 两种rhIL-2方案的免疫效果比较 加HAART与单独HAART。 ACTG 874子研究的次要目的是 淋巴结中HIV产生的细胞来源的评估 HAART治疗前后的组织，以及在HAART治疗前后 淋巴结组织与外源性rhIL-2的添加，在一个子集， 受试者（n=12）。 HIV疾病的特征是CD 4 T淋巴细胞的进行性下降 和增加病毒负荷， 核苷类似物。 然而，CD 4计数的这些改善确实 与临床获益相关，在某些情况下， 生存优势 即使在最有希望的研究中， HIV病毒RNA水平降低两个或更多个对数，或在改善的情况下， 观察了临床结局，然而，对CD 4细胞计数的影响 CD 4计数没有恢复到正常水平。 一个 开发有效治疗艾滋病毒的有吸引力的建议 这也可能刺激缺乏和功能失调的 免疫系统引起的艾滋病毒是使用强效抗逆转录病毒药物， 与细胞因子或其他免疫刺激因子结合，例如 白细胞介素-2（rhIL-2）。

The purpose of this ACTG protocol is to evaluate the effect of intermittent recombinant human interleukin-2 (rhIL-2) by intravenous or subcutaneous administraton in subjects with HIV infection on highly-active antiretroviral therapy (HAART) compared to HAART alone. The primary hypotheses include 1) that there will be a difference between different routes of intermittently administered rhIL-2 (IV vs subcutaneous admininistration) with a highly active antiretroviral regimen compared to highly active antiretroviral therapy alone with respect to the proportion of subjects achieving 50% increase in CD4 counts above pre-randomization baseline values after one year of rhIL-2 and the rate of change in CD4 counts; 2) that there will be a difference between the safety, tolerance, and effect on quality of life of these regimens, and 3) that there will be measureable changes in immune cell phenotypes and function and on HIV viral load and rate of antiviral drug resistance development when HAART is used in the setting of rhIL-2 compared to HAART alone. The ACTG 872 substudy has as a secondary hypothesis that there will be specific and different immunologic effects when comparing the two regimens of rhIL-2 plus HAART vs. HAART alone. The ACTG 874 substudy has as a secondary aim the assessment of the cellular source of HIV production in lymph node tissue before and after treatment with HAART, and the changes induced in lymph node tissue with the addition of exogenous rhIL-2, in a subset of subjects (n=12). HIV disease is characterized by a progressive decline in CD4 T-lymphocytes and increasing viral burden that are only marginally improved with the use of nucleoside analogues. These improvements in CD4 counts, however, do correlate with clinical benefit and, in some circumstances, with a survival advantage. Even in the most promising studies where peripheral HIV viral RNA levels are decreased by two or more logs or where improved clinical outcomes were observed, however, the effect on CD4 cell counts remained modest, and CD4 counts were not restored to normal levels. An attractive proposition for the development of effective treatment for HIV which may also stimulate reconstitution of the deficient and dysfunctional immune system caused by HIV is the use of potent antiretroviral drugs in conjunction with cytokines or other immune stimulatory factors such as interleukin-2 (rhIL-2).