IMMUNE REACTIVITY AND ONCOGENIC VIRUS INFECTION

免疫反应性和致癌病毒感染

• 批准号: 2894445
• 负责人: Martin S. Hirsch
• 金额: $ 27.62万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 2000-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2894445
• 关键词: 2'3' dideoxycytidine; 2'3' dideoxyinosine; AIDS; AIDS therapy; antiAIDS agent; combination chemotherapy; cytotoxic T lymphocyte; drug screening /evaluation; human immunodeficiency virus 1; human tissue; macrophage; microorganism immunology; tissue /cell culture; virulence; virus infection mechanism; virus replication; zidovudine

DESCRIPTION: (Adapted from investigator's abstract) Combination anti retroviral chemotherapy offers the most promising approach for sustained suppression of HIV-1 replication. By better understanding interactions among cells, virus and drugs, more effective combination strategies for prolonged HIV-1 inhibition will be developed. Specific aims of this project include the following: (1) To characterize host cellular factors, such as their state of activation, that modify responses to anti retroviral combinations. (2) To characterize viral pathogenetic factors, such as resistance genotype, syncytium-inducing phenotype, or viral load, that help to determine responses to anti retroviral combinations. (3) To characterize changes in anti-HIV-1 cell mediated immune responses in infected individuals in response to potent anti retroviral combination regimens. In vitro model systems, such as the CD4 cell outgrowth assay and the viral breakthrough replication assay will be utilized to mimic clinical conditions including acute infection, latency, and persistent productive infection. Resting cell versus activated cell models will be explored for both lymphocytes and monocyte/macrophages in order to develop strategies that can be tested in the clinic. Individualized combination strategies will be studied in patients who will be monitored for cell-mediated immune responses, e.g., cytotoxic T lymphocyte (CTL) activity, as well as for virus load. Decreases in HIV-1 load should be mirrored by increases in CTL activity, resulting in further synergy between therapy and immune responses. By combining in vitro and in vivo studies of combination regimens, it is believed that optimal therapeutic combination regimens can be developed for durable HIV-1 inhibition.

描述：（改编自研究者摘要）组合抗