Protection from HIV Infection in Intravenous Drug Users

预防静脉吸毒者感染艾滋病毒

• 批准号: 8100171
• 负责人: JAY A LEVY
• 金额: $ 19.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100171
• 关键词: Antiviral Response; Blood specimen; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Characteristics; Dendritic Cells; Development; Drug user; Enrollment; Epidemiology; Evaluation; Exposure to; HIV; HIV Infections; HIV vaccine; High Prevalence; Immune; Immune response; Individual; Infection; Injecting drug user; Interferons; Natural Immunity; Natural Killer Cells; Pilot Projects; Prevalence; Production; Regulatory T-Lymphocyte; Research; Research Proposals; Resistance to infection; Risk; Risk Behaviors; Risk Factors; Route; Testing; Work; high risk; high risk behavior; immune activation; intravenous drug user; pathogen; prevent; public health relevance; response; sex risk; transmission process

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。杰伊·利维（Jay Levy）和唐·德·贾拉（Don Des Jarlais）进行了一项试点研究，研究了暴露于HIV的大量注射吸毒者（IDU）不会被感染。该保护的原因尚不清楚，但他们假设它可能与先天免疫反应有关。这种类型的免疫活性在与病原体相互作用后迅速发生，它通过非传播传播途径保护了其他人暴露于HIV的个体（见下文）。在试点研究中，有30个未感染的IDU（23％）中有7个显示了先天CD8+细胞抗HIV反应。这种CD8+细胞非毒性抗病毒反应（CNAR）仅在暴露于或感染HIV的人中。 CNAR可能负责这种保护免受感染。该提案的目的是对IDU的这一重要观察进行深入研究。其中包括进一步评估IDU中高风险行为与CNAR的关联，并探索其他先天免疫活性，尤其是浆细胞类动物树突状细胞和NK细胞和免疫激活作为影响感染抗性的可能因素。拟议的研究的具体目的如下：1。确定CD8+细胞非毒性抗病毒药反应（CNAR）在HIV血清染色性IDU中的患病率（CNAR）的患病率很高，最近（过去一年）通过性风险行为暴露于HIV的近期（过去一年）艾滋病毒的可能性很高。我们将检验以下假设：与最近对CNAR的近期接触近期艾滋病毒的可能性高，与近期风险的风险低相比，CNAR的患病率更高，而对HIV的性风险则低。 2。确定其他先天性抗HIV特征，例如NK细胞的数量，浆细胞类动物树突状细胞和免疫激活是否与HIV血清神经IDU的潜在保护相关。这些目标将通过从160名受试者中获取危险因素研究的160名受试者的其他血液样本来实现：80个IDU具有高注射率和低性风险的近期HIV暴露，40个IDU，低注射且性较低的性风险，20 HIV阴性的非注射非注射药物使用者，20 HIV SERPERSIDER IDU。我们的飞行员工作表明，大约四分之一的注射吸毒者可能具有先天免疫反应，可以防止艾滋病毒感染。了解这种先天的免疫反应可能会在注射吸毒者中对HIV的流行病学有很大贡献，并可能为开发新的HIV感染疗法和可能的HIV疫苗提供关键信息。 公共卫生相关性：该项目侧重于自然免疫抗病毒反应，这些反应对于防止艾滋病毒感染并因此限制了其在全球范围内的传播至关重要。