STUDY OF SUBCUTANEOUS RECOMBINANT IL-2 IN PATIENTS WITH HIV-1 INFECTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。晚期疾病患者在开始抗逆转录病毒治疗后免疫功能的不完全恢复是早期使用抗逆转录病毒药物的一个理由。然而，抗逆转录病毒治疗对早期无症状艾滋病患者的临床益处尚未用目前的临床策略进行评估。在这个疾病阶段，临床医生和患者面临着一个重大的困境，因为现有的治疗方法在短期内，甚至可能在几年内都非常有效。然而，由于毒性和耐药性的发展，在发生严重机会性疾病的风险最大的时候到来之前，现有的抗逆转录病毒治疗有很大的用尽风险。通过白细胞介素-2直接扩增CD4+淋巴细胞来维持免疫功能，可能是HIV管理的重要补充策略。此外，最近有人推测IL-2联合强效抗逆转录病毒治疗可能是清除潜伏感染的CD4+细胞中的HIV的有效方法。在ESPRIT中测试的假设是，在HIV感染的早期阶段（CD4+计数大于或等于300个细胞/mm3）， IL-2治疗联合抗逆转录病毒治疗的干预将防止CD4+ T细胞耗损，并导致比单独抗逆转录病毒治疗更少的艾滋病定义疾病。重组白细胞介素-2 (il -2)，商品名为Proleukin，是一种有效的免疫调节剂，目前被许可用于治疗转移性天然蛋白，对来自HIV患者的细胞具有强大的体外作用。关键是，IL-2诱导t淋巴细胞和b淋巴细胞的增殖，增强对多种靶细胞的细胞溶解活性，增加自然杀伤细胞的功能。最初的临床研究结合实验室评估确定了最佳诱导CD4+ t淋巴细胞增殖的方案。基于每8周5天的治疗方案，对HIV感染患者间歇性给予il -2，目前已经在多个试验中进行了检验。这些研究表明，这种治疗方案引起外周血CD4+细胞计数显著和持续的增加。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The incomplete recovery of immune function after initiation of antiretroviral therapy among patients with advanced disease is an argument for early use of antiretroviral drugs. However, the clinical benefit of antiretroviral therapy for patients with early, asymptomatic HIV disease has not been evaluated with current clinical strategies. At this disease stage, clinicians and patients face a major dilemma since available therapies are very potent in the short-term, perhaps even for several years. However, due to toxicities and the development of drug resistance, there is substantial risk of exhaustion of available antiretroviral treatments before the time when the risk of serious opportunistic diseases is greatest. Preservation of immune function by direct expansion of CD4+ lymphocytes with interleukin-2, could represent a significant additional strategy for the management of HIV. In addition, it has recently been speculated that IL-2 in combination with potent antiretroviral therapy may be a useful approach for purging HIV from the latently infected CD4+ cells. The hypothesis being tested in ESPRIT is that intervention with IL-2 therapy in combination with antiretroviral therapy at an early stage of HIV infection (CD4+ counts greater than or equal to 300 cells/mm3) will prevent CD4+ T cell depletion and result in fewer AIDS defining illnesses than antiretroviral therapy alone. Recombinant interleukin-2 (rIL-2), with the trade name Proleukin, is a potent immunomodulator currently licensed for the treatment of metastatic natural protein exerts potent in vitro effect on cells derived from patients with HIV. Critically, IL-2 induces proliferation of T-lymphocytes and B-lymphocytes, enhances cytolytic activity against a variety of target cells and increases natural killer cell function. Initial clinical studies coupled with laboratory evaluations identified a regimen for optimal induction of CD4+ T-lymphocyte proliferation. Intermittent administration of rIL-2 to patients with HIV infection based upon a regimen delivered for five days every eight weeks has now been examined in multiple trials. These studies have revealed that this regimen gives rise to significant and sustained increases in peripheral CD4+ cell counts.