ANTIHIV T CELL RESPONSES DURING ANTIVIRAL DRUG THERAPY

描述：（改编自申请人的摘要）在最后一个编号中， 几个月来，HIV-1感染的临床病程有了显着改善， 在接受联合抗病毒药物治疗的患者中有记录 在一个实施方案中，本发明的化合物用于治疗癌症，并且包括蛋白酶抑制剂和核苷抑制剂。 在几项研究中，大约85%的患者显示2-3 log HIV-1血浆载量减少，CD 4 T细胞显著增加， 在没有临床艾滋病的情况下接受治疗至少一年的人数。 根据茚地那韦（默克035）试验的初步结果， 有效的抗病毒治疗一年的结果只有部分恢复， 抗HIV-1细胞毒性T淋巴细胞（CTL）免疫，其对以下具有选择性： 某些病毒蛋白 T细胞对HIV-1和非HIV-1的识别反应 抗原不能完全重构。 因为T细胞免疫可能是一种 保护HIV-1感染的主要相关因素， 抗病毒药物治疗可能部分取决于完全恢复 抗HIV-1 CD 8 + CTL和CD 4 + T辅助细胞应答。 PI假设 这种恢复可以通过靶向宿主 树突状细胞（DC）与某些形式的HIV-1抗原，将激活 幼稚T细胞和扩展记忆CTL和T辅助细胞， HIV-1特异性。 本提案的具体目标是：（1）界定 HIV-1特异性CD 8+和CD 4 + T细胞应答 治疗，包括HIV-1表位描绘，T细胞表型和T细胞 受体库;（2）确定DC-抗原递送的功效 用于HIV-1蛋白和基因的最佳体外刺激的系统 HIV-1初治受试者中的原发性CD 4+和CD 8 + T细胞应答;（3）恢复 并增强HIV-1特异性CD 4 + T辅助细胞和CD 8 + CTL的反应， 体外，在HIV-1感染患者中使用基于DC的抗原递送系统 治疗后有部分，有限的免疫反应， 联合抗逆转录病毒药物

DESCRIPTION: (Adapted From Applicant's Abstract) In the last number of months, dramatic improvements in the clinical course of HIV-1 infection have been documented in patients who are treated with combined antiviral drug therapy and includes a protease inhibitor and nucleoside inhibitors. Approximately 85% of many patients in several studies show a 2-3 log decrease in HIV-1 plasma load, and significant increases in CD4 T-cell numbers in the absence of clinical AIDS for at least one year on therapy. Based on the preliminary results in a trial with Indinavir (Merck 035), potent antiviral therapy for one year results in only partial recovery of anti-HIV-1 cytotoxic T-lymphocyte (CTL) immunity that is selective for certain viral proteins. T-cell recognition responses to HIV-1 and non-HIV-1 antigens are not fully reconstituted. Because T-cell immunity may be a major correlate of protection in HIV-1 infection, the efficacy of antireroviral drug therapy may in part depend on restoration of complete anti-HIV-1 CD8+ CTL and CD4+ T helper cell responses. The PI hypotheses that such restoration can be achieved with therapy by targeting host dendritic cells (DC) with certain forms of HIV-1 antigens that will activate naive T-cells and expand memory CTL and T-helper cells with HIV-1-specificity. The specific aims of this proposal are to: (1) define the HIV-1-specific CD8+ and CD4+ T-cell responses pre- and post-combined therapy, including HIV-1 epitope delineation, T-cell phenotyping and T-cell receptor repertoire; (2) to determine the efficacy of DC-antigen delivery systems for HIV-1 proteins and genes for optimal in vitro stimulation of primary CD4+ and CD8+ T-cell responses in HIV-1-naive subjects; (3) restore and enhance HIV-1-specific responses of CD4+ T helper cells and CD8+ CTL in vitro, using DC-based antigen delivery systems in HIV-1-infected patients who have a partial, limited immunological response after treatment with combined antiretrovirals.