IMMUNE REACTIVITY AND ONCOGENIC VIRUS INFECTIONS

本项目的长期目标是阐明相互作用 在HIV-1、人类白细胞和免疫反应性之间， 利用这些信息来防止 感染，即艾滋病的发展。具体目标是 项目期内都是开发新的策略组合使用 治疗HIV-1感染，确定药物失败的机制 在长期治疗后，描述HIV-1表型的演变， 基因型在各种形式的治疗，并表征的影响， HIV-1特异性细胞毒性T淋巴细胞（CTL）的抗病毒治疗 反应性 实验也将在培养的感染细胞上进行 如来自受感染患者的样本。组合和 将采用涉及核苷的序贯治疗方案 (ddi、AZT、ddc）以及其它药剂（rIFN α A、蛋白酶 抑制剂、非核苷逆转录酶抑制剂）。 将评价治疗期间的突破性病毒的基因型 改变和表型特征（例如，合胞体容量， 细胞向性）。将对长期治疗方案的细胞进行评价 对药物无效分子间相互作用 将探索联合用药。CTL活性将是 在接受治疗的患者中进行前瞻性测量，以及药物的作用 或药物组合对CTL活性的影响。这些研究 应该有助于形成更合理的抗HIV-1组合的基础 治疗在未来几年。

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.