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)：Jay Levy博士和Don des Jarlais博士进行了一项初步研究，考察了相当大比例的注射吸毒者(IDU)接触艾滋病毒后不会感染的可能性。这种保护的原因尚不清楚，但他们推测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，保护了通过非静脉传播途径接触艾滋病毒的其他人(见下文)。在初步研究中，30名未感染的注射吸毒者中有7名(23%)显示出天生的CD8+细胞抗HIV反应。这种CD8+细胞非细胞毒性抗病毒反应(CNAR)仅在接触或感染艾滋病毒的人中观察到。CNAR可能负责这种免受感染的保护。这项提议的目的是对注射吸毒者的这一重要观察结果进行深入研究。包括对注射吸毒者的高危行为与CNAR的相关性的进一步评估，并探索其他先天免疫活动，特别是浆细胞样树突状细胞和NK细胞的免疫活性以及免疫激活作为影响感染抵抗力的可能因素。这项研究的具体目的如下：1.确定最近(过去一年)通过注射危险行为接触艾滋病毒的可能性很高，而通过性行为接触艾滋病毒的可能性较低的血清阴性注射吸毒者中CD8+细胞非细胞毒性抗病毒反应(CNAR)的流行率。我们将检验这一假设，即通过注射危险行为最近接触艾滋病毒的可能性较高的注射吸毒者将比最近注射风险较低且接触艾滋病毒的性风险较低的注射吸毒者有更高的CNAR患病率。2.确定其他先天抗HIV特征，如NK细胞、浆细胞样树突状细胞和免疫激活是否与HIV血清阴性注射人群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获得额外的血液样本来实现：80名最近接触艾滋病毒的高注射和低性风险的注射吸毒者，40名低注射和低性风险的注射吸毒者，20名艾滋病毒阴性的非注射吸毒者和20名艾滋病毒血清阳性的注射吸毒者。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先天免疫反应，可以预防艾滋病毒感染。了解这种先天免疫反应可大大有助于了解注射吸毒者中的艾滋病毒流行病学，并可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。 与公共卫生相关：该项目侧重于自然免疫抗病毒反应，这对预防艾滋病毒感染从而限制其在世界各地的传播可能非常重要。