IMMUNE REACTIVITY AND ONCOGENIC VIRUS INFECTIONS

该项目的长期目标是澄清相互作用 在HIV-1、人类白细胞和免疫反应性之间，目标是 利用这些信息来预防 感染，即艾滋病的发展。这方面的具体目标 项目期内正在制定新的使用策略相结合 HIV-1感染的治疗，确定药物失败的机制 在长期治疗后，描述HIV-1表型的演变和 在不同形式的治疗中的基因类型，并表征其效果 抗病毒治疗对HIV-1特异性细胞毒性T淋巴细胞(CTL)的影响 反应性。 实验也将在培养中的受感染细胞上进行。 与从感染患者身上提取的标本相同。组合和 将采用涉及核苷的序贯治疗方案 (DDI、AZT、DDC)以及其他试剂(r干扰素αA、蛋白酶 非核苷逆转录酶抑制剂)。 将对治疗过程中的突破性病毒进行基因分型评估 改变和表型特征(例如，合胞体能力， 细胞嗜性)。来自延长治疗方案的细胞将被评估 对有问题的药物的耐受性。分子间的相互作用 将探索联合用药。CTL活动将是 前瞻性测量患者对治疗的影响以及药物的效果 或药物组合对CTL活性的影响将被检查。这些研究 应有助于形成更合理的抗HIV-1组合的基础 未来几年的治疗。

The long term objectives of this project are to clarify interactions among HIV-1, human leukocytes, and immune responsiveness, with the goal of utilizing this information to prevent the pathogenic consequences of infection, i.e. the development of AIDS. The specific aims for this project period are to develop new strategies for the use of combination therapy for HIV-1 infection, determine the mechanisms for drug failure after prolonged therapy, describe the evolution of HIV-1 phenotypes and genotypes during various forms of therapy, and characterize the effects of antiviral treatments on HIV-1 specific cytotoxic T lymphocyte (CTL) reactivity. Experiments will be conducted both on infected cells in culture as well as on specimens derived from infected patients. Combination and sequential treatment regimens will be employed involving nucleosides (ddi, AZT, ddc) as well as other agents (rIFN alpha A, protease inhibitors, non-nucleoside reverse transcriptase inhibitors). Breakthrough viruses during therapy will be evaluated for genotypic alterations and phenotypic characteristics (e.g., syncytium capacity, cell tropism). Cells from prolonged treatment regimens will be evaluated for refractoriness to the drug in question. Molecular interactions among drugs in combination will be explored. CTL activity will be prospectively measured in patients on therapy, and the effects of drugs or drug combinations on CTL activity will be examined. These studies should help form the basis for more rational anti-HIV-1 combination therapy in future years.