SAFETY AND ANTIVIRAL EFFICACY OF IMMUNOTHERAPY WITH AUTOLOGOUS CD8+ HIV-SPECIFIC

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。 高效抗逆转录病毒疗法（HAART）可以将HIV复制抑制到无法检测的水平。然而，即使经过多年不间断的治疗，一旦HAART停止，病毒复制迅速重新启动，并发生疾病进展。HAART个体中的病毒持续存在部分是由于受感染的静息CD4 + T细胞池的长期存活以及尽管HAART抑制，但仍存在低水平的HIV复制。这种病毒更替可以解释高效抗逆转录病毒疗法下艾滋病毒库的不断补充。进一步的研究表明，肠道和淋巴组织是这种水库的主要网站。这项I/II期临床研究提出通过过继转移大量HIV特异性CD8 + T细胞来靶向HAART患者中正在进行的HIV复制部位。将评价转移的CD8 + T细胞对低病毒负荷患者（最可能接受HAART）HIV+复制的安全性和疗效。将确定14天疗程的低剂量s.c. IL-2可以促进转移细胞的持久性和抗病毒活性，如黑素瘤特异性CD8 + T细胞克隆的过继转移研究所示。将HIV特异性CD8 + T细胞定位于残留病毒复制的已知位点与作为对照的CMV特异性克隆的伴随输注进行比较。我们计划以1个月的间隔向10名患者给予3.3 × 109/m2的HIV和CMV克隆细胞，第二次输注，随后进行14天的s.c. IL-2。

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. Highly active antiretroviral therapy (HAART) can suppress HIV replication to undetectable levels. However, even after years of uninterrupted therapy and as soon as HAART is stopped, viral replication is rapidly reinitiated and progression to disease occurs. Viral persistence in individuals on HAART is due, in part, to the long-term survival of a pool of infected, resting CD4+ T cells and to low levels of ongoing HIV replication despite HAART suppression. This viral turnover could account for the constant replenishment of the HIV reservoir under HAART. Further studies have shown that gut and lymphoid tissues are major sites for such reservoirs. This phase I/II clinical study proposes to target sites of ongoing HIV replication in patients on HAART by the adoptive transfer of large amounts of HIV-specific CD8+ T cells. The safety and efficacy of transferred CD8+ T cells on HIV+ replication in patients with low viral burdens, most likely receiving HAART, will be evaluated. It will be determined if the administration of a 14 day course of low-dose s.c. IL-2 can promote the persistence and antiviral activity of transferred cells, as shown in adoptive transfer studies of melanoma-specific CD8+ T cell clones. The localization of HIV-specific CD8+ T cells to known sites of residual viral replication will be compared to the concomitant infusion of a CMV-specific clone used as a control. We plan to administer 3.3 x 109/m2 cells of an HIV and a CMV clone to 10 patients with a 1 month interval, the second infusion followed by 14 days of s.c. IL-2.