INTERLEUKIN-2 (IL-2) THERAPY WITH ANTIRETROVIRAL THERAPY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 1.确定高效抗逆转录病毒治疗（HAART）与联合HAART和超低剂量白细胞介素-2（IL-2）免疫治疗相比，对早期HIV感染的抑制程度。 假设： a. 早期HAART将消除未整合的前病毒库，并减缓PBMC和淋巴结中整合的潜在感染性潜伏库HIV的建立。 B. IL-2免疫治疗可增加和延长HIV特异性CTL。 C. 病毒载量（血浆RNA、整合DNA和未整合DNA）的大小与早期HIV分离株的适应性（复制能力）和耐药性相关。 D. HIV复制和疾病进展的抑制将与PBMC对内源性和外源性病毒生长的体外抗性的建立相关。 2. 评价早期HIV感染时免疫系统损伤的程度，以及HAART单独治疗与HAART+超低剂量IL-2联合治疗对免疫系统恢复的影响。 假设条件： a. 急性HIV感染导致记忆细胞的耗竭和T细胞库中的“洞”的发展。 B. 即使在早期HIV感染中，IL-12的产生也是有缺陷的，这种缺陷是由补体-CD 46相互作用介导的，类似于麻疹感染中所见。 C. IL-2可降低损伤程度，加速免疫系统恢复。 3. 建立血浆、血清、外周血和淋巴结单核细胞以及HIV-1分离株标本库，用于进一步研究HIV发病机制。 研究方法： 这是一项前瞻性、观察性和干预性研究，对象是急性感染艾滋病毒（< 2个月）或最近感染艾滋病毒（2 - 12个月）的人。 预计每年将招募30-50名最近的HIV-1血清转换者用于研究，包括10-15名急性感染者，年龄> 13岁，约70%为男性，25%为非西班牙裔白人，75%为非洲裔美国人，在马里兰州的巴尔的摩。 参与者可以选择接受或不接受高效抗逆转录病毒治疗（HAART）。 未接受HAART治疗的受试者将作为接受HAART治疗的受试者的对照组。 将使用各种实验室技术，包括流式细胞术、淋巴细胞增殖试验、病毒分离和病毒库定量，研究HAART对免疫系统完整性的影响，以及HAART开始时，作为感染持续时间的函数，HAART对免疫系统完整性恢复的影响。

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. 1. To determine the extent of suppression of early HIV infection achieved by highly active antiretroviral therapy (HAART) compared to combined HAART and immunotherapy with ultralow-dose interleukin-2 (IL-2). Hypotheses: a. Early HAART will eliminate the unintegrated proviral reservoir and slow the establishment of the integrated, potentially infectious latent reservoir HIV in PBMC and lymph nodes. b. IL-2 immunotherapy will augment and prolong HIV-specific CTL. c. The magnitude of viral load (plasma RNA, integrated DNA, and unintegrated DNA) correlates with the fitness (replicative capacity) and drug resistance of the early HIV isolate. d. Suppression of HIV replication, and disease progression, will correlate with establishment of in vitro resistance of PBMC to endogenous and exogenous virus growth. 2. To evaluate the extent of immune system damage that occurs in early HIV infection, and the effect of HAART alone vs. combined HAART plus ultralow-dose IL-2 on immune system recovery. Hypotheses: a. Acute HIV infection leads to depletion of memory cells and development of "holes" in the T cell repertoire. b. IL-12 production is defective even in early HIV infection, and this defect is mediated by a complement-CD46 interaction similar to that seen in measles infection. c. IL-2 reduces the extent of damage and accelerates immune system recovery. 3. To establish a repository of specimens of plasma, serum, peripheral blood and lymph node mononuclear cells, and HIV-1 isolates that can be used for additional studies of HIV pathogenesis. METHODOLOGY: This is a prospective, observational, and interventional study of people who have been acutely infected with HIV (< 2 month) or recently (2 - 12 months). It is anticipated that 30-50 recent HIV-1 seroconverters per year will be recruited for the study, including 10-15 who have been acutely infected, ranging in age from > 13 years, approximately 70% male, 25% non-Hispanic whites and 75% African-American, in Baltimore, Maryland. Participants may elect to receive or not receive highly active antiretroviral therapy (HAART). Participants who do not receive HAART will serve as a comparison group for those who do receive HAART. The effect of HAART on immune system integrity will be studied, as well as the effect of HAART on the recovery of immune system integrity as a function of the duration of infection at the time when HAART is started, using a variety of laboratory techniques including flow cytometry, lymphocyte proliferative assays, viral isolation, and quantitation of viral reservoirs.