STUDIES ON THE ROLE OF INTERLEUKIN-2 IN THE MANAGEMENT OF HIV INFECTION

IL-2 在 HIV 感染治疗中作用的研究

• 批准号: 6289384
• 负责人: JOSEPH A KOVACS
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289384
• 关键词: AIDS therapy; HIV infections; antiAIDS agent; antiviral agents; clinical research; clinical trials; combination chemotherapy; drug administration rate /duration; drug tolerance; human immunodeficiency virus; human subject; human therapy evaluation; immunomodulators; immunotherapy; interleukin 2; leukocyte count

Interleukin-2 (IL-2) is a cytokine with important regulatory properties for both T and B cells. The current studies were undertaken to evaluate IL-2 in the treatment of human immunodeficiency virus (HIV) infection. Our studies initially focused on patients with CD4 counts about 200 cells/cu mm, administering IL-2 for 5 days approximately every 2 months at doses ranging from 6 to 18 million units/d. The courses of IL-2 were well tolerated, although most of the patients required dosage reductions due to IL-2-related adverse effects. Sustained improvement in CD4 number was seen primarily in patients with >200 CD4 cells/cu mm. There also was a transient increase in viral load as measured by the bDNA assay seen at day 6 to day 8 following initiation of IL-2 therapy. Responses in CD4 number were less common in patients with lower baseline CD4 counts. Based on the preliminary results seen in our open trial, we undertook a randomized trial to evaluate IL-2 therapy in patients with CD4 counts above 200 cells/cu mm in combination with currently approved antiretroviral therapies. The study opened in April 1993 and was completed in February of 1995, with 60 patients enrolling. This study also showed in a controlled setting that intermittent therapy with IL-2 can lead to a substantial and sustained increase in CD4 cell counts without leading to an increase in plasma viral load. More recently, we have focused on improving the tolerance of IL-2, by decreasing the dose and duration of therapy, and by evaluating alternative methods of administering IL-2. We have been enrolling patients in an extension phase of ongoing studies to determine whether administration of corticosteroids with IL-2 can lead to improved tolerance of IL-2 with-out interfering with the immunomodulatory effects. Preliminary experience has shown that in some patients previously unresponsive to IL-2, improved tolerance of IL-2 when it was coadministered with prednisone has allowed dose escalation of IL-2 and resulted in an increase in CD4 counts. Prednisone is currently being held, however, as we evalu-ate the potential role of steroids in the development of avascular necrosis in HIV-infected patients. These studies are potentially important because they are the first ones to suggest that immunomodulating agents combined with antiretroviral agents may have a benefit in patients with HIV infection.

白介素-2（IL-2）是T和B细胞具有重要调节特性的细胞因子。目前的研究是为了评估IL-2治疗人类免疫缺陷病毒（HIV）感染的研究。我们的研究最初集中在CD4患者中，约有200个细胞/CU mM，每2个月每2个月施用5天的IL-2，范围为6至1800万单位/d。 IL-2的课程耐受性良好，尽管大多数患者由于IL-2相关的不良反应而需要降低剂量。 > 200 CD4细胞/CU MM的患者主要看到CD4数量的持续改善。通过IL-2治疗开始后的第6到第8天，病毒载量也瞬时增加。在较低的基线CD4计数患者中，CD4数量的反应不太常见。根据在开放试验中看到的初步结果，我们进行了一项随机试验，以评估200个细胞/CU MM高于200细胞/CU MM的患者的IL-2治疗，并结合当前批准的抗逆转录病毒疗法。这项研究于1993年4月开放，于1995年2月完成，有60名患者参加。这项研究还表明，在受控的环境中，使用IL-2进行间歇性治疗会导致CD4细胞计数的大幅增长，而不会导致血浆病毒载量增加。最近，我们通过减少治疗的剂量和持续时间以及评估施用IL-2的替代方法来提高IL-2的耐受性。我们一直在正在进行的研究的扩展阶段中招募患者，以确定施用IL-2的皮质类固醇是否会导致IL-2的耐受性提高，从而干扰免疫调节作用。初步经验表明，在某些以前对IL-2的患者中，与泼尼松共同促成IL-2的耐受性提高了IL-2的耐受性，允许IL-2剂量升级，并导致CD4计数增加。但是，当我们评估类固醇在HIV感染患者中的潜在作用中，目前正在持有泼尼松。这些研究可能很重要，因为它们是第一个表明与抗逆转录病毒药物结合的免疫调节剂可能对HIV感染患者有好处的研究。