IV OR SQRHIL2 IN HIV INFECTED SUBJECTS ON HAART

该ACTG方案的目的是评估 间歇性静脉或静脉注射重组人白细胞介素2 高效氯丙沙星对HIV感染者的皮下注射 抗逆转录病毒治疗(HAART)与单独使用HAART进行比较。初级阶段 假设包括1)不同的 间歇给药途径(静脉注射与皮下注射比较) 管理)与高效抗逆转录病毒疗法相比 单用高效抗逆转录病毒治疗的比例 在随机化前CD4细胞增加50%的受试者中 重组人白细胞介素2治疗一年后的基线值和CD4的变化率 2)在安全性、耐受性、 以及对这些养生方法的生活质量的影响，以及3)将有 免疫细胞表型和功能的可测量变化与艾滋病毒 HAART时的病毒载量和抗病毒耐药性的发展速度 与单独使用HAART相比，用于设置rhIL-2。ACTG 872 子研究有一个次要假设，即将有具体的和 比较两种重组人白细胞介素2方案的免疫效果 加上HAART与单独的HAART。ACTG 874分研究有一个次要目标 淋巴结中HIV产生的细胞来源的评估 HAART治疗前后的组织学变化 淋巴组织中添加外源重组人白介素2 受试者12例。 HIV疾病的特征是CD4T淋巴细胞进行性下降 以及增加的病毒负担，这些负担仅因使用而略有改善 核苷类似物。然而，CD4计数的这些改善确实起到了 与临床益处相关，在某些情况下，还与 生存优势。即使在最有希望的研究中，外围设备 HIV病毒RNA水平下降两个或更多个对数或改善 临床结果被观察到，然而，对cd4细胞计数的影响。 仍保持温和，CD4计数没有恢复到正常水平。一个 开发有效的艾滋病毒治疗方法的诱人建议 这也可能刺激缺陷和功能障碍的重建 由HIV引起的免疫系统是使用有效的抗逆转录病毒药物 与细胞因子或其他免疫刺激因子结合，如 白介素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).