Protection from HIV Infection in Intravenous Drug Users
预防静脉吸毒者感染艾滋病毒
基本信息
- 批准号:8012878
- 负责人:
- 金额:$ 25.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:Antiviral ResponseBlood specimenCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCellsCharacteristicsDendritic CellsDevelopmentEnrollmentEpidemiologyEvaluationExposure toHIVHIV InfectionsHIV vaccineHigh PrevalenceImmuneImmune responseIndividualInfectionInjecting drug userInjection of therapeutic agentInterferonsIntravenousNatural ImmunityNatural Killer CellsPilot ProjectsPrevalenceProductionRegulatory T-LymphocyteResearchResearch ProposalsResistance to infectionRiskRisk BehaviorsRisk FactorsRouteTestingWorkhigh riskhigh risk behaviorimmune activationintravenous drug userpathogenpreventpublic health relevanceresponsesex risktransmission process
项目摘要
DESCRIPTION (provided by applicant): Drs. Jay Levy and Don Des Jarlais have conducted a pilot study examining the possibility that a substantial percentage of injection drug users (IDUs) exposed to HIV do not become infected. The reason for this protection is not known, but they hypothesize that it could be related to innate immune responses. This type of immune activity, which occurs rapidly after interacting with a pathogen, has protected other individuals exposed to HIV by non-intravenous routes of transmission (see below). In the pilot study, seven of thirty uninfected IDUs (23%) showed an innate CD8+ cell anti-HIV response. This CD8+ cell noncytotoxic antiviral response (CNAR) has only been observed in people exposed to or infected by HIV. CNAR could be responsible for this protection from infection. The purpose of this proposal is to conduct an in-depth study of this important observation on IDUs. Included is further evaluation of the association of high-risk behavior in IDUs to CNAR, and to explore other innate immune activities, particularly those of plasmacytoid dendritic cells and NK cells and immune activation as possible factors that influence resistance to infection. The Specific Aims of the proposed research are as follows: 1. Determine the prevalence of the CD8+ cell noncytotoxic antiviral response (CNAR) among HIV seronegative IDUs with a high likelihood of recent (past year) exposure to HIV through injecting risk behavior and with low likelihood of exposure to HIV through sexual risk behavior. We will test the hypothesis that IDUs with a high likelihood of recent exposure to HIV through injecting risk behavior will have a higher prevalence of CNAR than will IDUs with a low recent risk for injecting risk and low sexual risk exposure to HIV. 2. Determine whether other innate anti-HIV characteristics, such as the number of NK cells, plasmacytoid dendritic cells and immune activation are associated with potential protection from infection in HIV seronegative IDUs. These aims will be achieved by obtaining additional blood samples from 160 subjects to be enrolled in the Risk Factors study: 80 IDUs with high injecting and low sexual risk for recent HIV exposure, 40 IDUs, with low injecting and low sexual risk, 20 HIV negative non-injecting drug users, and 20 HIV seropositive IDUs. Our pilot work indicates that approximately one quarter of injecting drug users may have innate immune responses that can protect against HIV infection. Understanding such innate immune responses could contribute greatly to the epidemiology of HIV among injecting drug users and may provide critical information for the development of new therapies for HIV infection and a possible HIV vaccine.
PUBLIC HEALTH RELEVANCE: This project focuses on natural immune anti-viral responses that can be important in preventing HIV infection and thus limiting its spread throughout the world.
描述(由申请人提供): Drs. Jay Levy 和 Don Des Jarlais 进行了一项试点研究,检验了相当一部分接触 HIV 的注射吸毒者 (IDU) 没有被感染的可能性。这种保护的原因尚不清楚,但他们假设这可能与先天免疫反应有关。这种类型的免疫活动在与病原体相互作用后迅速发生,保护了其他通过非静脉传播途径接触艾滋病毒的个体(见下文)。在试点研究中,30 名未感染的注射吸毒者中有 7 名 (23%) 显示出先天的 CD8+ 细胞抗 HIV 反应。这种 CD8+ 细胞非细胞毒性抗病毒反应 (CNAR) 仅在暴露于或感染 HIV 的人群中观察到。 CNAR 可能负责这种免受感染的保护。本提案的目的是对这一关于注射吸毒者的重要观察结果进行深入研究。其中包括进一步评估注射吸毒者高危行为与 CNAR 之间的关联,并探索其他先天免疫活性,特别是浆细胞样树突状细胞和 NK 细胞的活性,以及免疫激活作为影响抗感染性的可能因素。拟议研究的具体目标如下: 1. 确定 HIV 血清阴性注射吸毒者中 CD8+ 细胞非细胞毒性抗病毒反应 (CNAR) 的流行情况,这些注射吸毒者近期(过去一年)通过注射危险行为接触 HIV 的可能性很高,且感染率较低。通过危险性行为接触艾滋病毒的可能性。我们将检验以下假设:近期通过注射危险行为接触 HIV 的可能性较高的 IDU 的 CNAR 患病率高于近期注射风险和性风险接触 HIV 风险较低的 IDU。 2. 确定其他先天抗 HIV 特征,例如 NK 细胞、浆细胞样树突状细胞和免疫激活的数量,是否与 HIV 血清阴性注射吸毒者免受感染的潜在保护有关。这些目标将通过从 160 名参加风险因素研究的受试者中获取额外的血液样本来实现:80 名注射吸毒者,近期艾滋病毒暴露量高且性风险低;40 名注射吸毒者,注射量低且性风险低;20 名艾滋病毒阴性非注射吸毒者和 20 名 HIV 血清阳性注射吸毒者。我们的试点工作表明,大约四分之一的注射吸毒者可能具有可预防艾滋病毒感染的先天免疫反应。了解这种先天免疫反应可以极大地促进注射吸毒者中艾滋病毒的流行病学,并可能为开发艾滋病毒感染的新疗法和可能的艾滋病毒疫苗提供关键信息。
公共卫生相关性:该项目重点关注自然免疫抗病毒反应,这对于预防艾滋病毒感染并限制其在世界范围内的传播非常重要。
项目成果
期刊论文数量(0)
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JAY A LEVY其他文献
JAY A LEVY的其他文献
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{{ truncateString('JAY A LEVY', 18)}}的其他基金
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新型抗 HIV 免疫蛋白的表征
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HIV Cure with CCr5 (-) Human IPS Hematopoietic Stem Cells
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HIV Cure with CCr5 (-) Human IPS Hematopoietic Stem Cells
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9052116 - 财政年份:2014
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HIV cure with CCR5 (-) human IPS hematopoietic stem cells
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- 批准号:
8470397 - 财政年份:2012
- 资助金额:
$ 25.53万 - 项目类别:
Protection from HIV Infection in Intravenous Drug Users
预防静脉吸毒者感染艾滋病毒
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8100171 - 财政年份:2010
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$ 25.53万 - 项目类别:
Role of Innate Immunity in Controlling HIV Infection
先天免疫在控制 HIV 感染中的作用
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7894208 - 财政年份:2009
- 资助金额:
$ 25.53万 - 项目类别:
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