Protection from HIV Infection in Intravenous Drug Users

预防静脉吸毒者感染艾滋病毒

• 批准号: 8012878
• 负责人: JAY A LEVY
• 金额: $ 25.53万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8012878
• 关键词: Antiviral Response; Blood specimen; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Characteristics; Dendritic Cells; Development; Enrollment; Epidemiology; Evaluation; Exposure to; HIV; HIV Infections; HIV vaccine; High Prevalence; Immune; Immune response; Individual; Infection; Injecting drug user; Injection of therapeutic agent; Interferons; Intravenous; 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博士进行了一项试点研究，研究了相当大比例的注射毒品使用者（IDUs）接触艾滋病毒后不受感染的可能性。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）。在初步研究中，30名未感染的注射吸毒者中有7名（23%）表现出先天性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HIV的人群中观察到。CNAR可能负责这种保护免受感染。本建议的目的是对关于注射吸毒者的这一重要意见进行深入研究。包括进一步评价注射吸毒者高危行为与CNAR的相关性，并探索其他先天性免疫活动，特别是浆细胞样树突状细胞和NK细胞的活动以及免疫活化作为影响感染抵抗力的可能因素。本研究的具体目的如下：1.确定最近（过去一年）通过注射风险行为暴露于HIV的可能性较高和通过性风险行为暴露于HIV的可能性较低的HIV血清阴性注射吸毒者中CD8+细胞非细胞毒性抗病毒应答（CNAR）的流行率。我们将检验这样的假设，即最近通过注射风险行为暴露于艾滋病毒的可能性高的注射吸毒者的CNAR患病率将高于最近注射风险低和性风险暴露于艾滋病毒的注射吸毒者。2.确定其他先天性抗HIV特征，如NK细胞数量、浆细胞样树突状细胞和免疫激活是否与HIV血清阴性IDUs的潜在感染保护相关。为实现这些目标，将从拟参加风险因素研究的160名受试者中获取额外的血液样本：80名注射吸毒者近期接触艾滋病毒的风险高，性风险低，40名注射吸毒者的风险低，性风险低，20名艾滋病毒阴性的非注射吸毒者，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毒品使用者可能具有先天免疫反应，可以防止艾滋病毒感染。了解这种先天免疫反应可大大有助于艾滋病毒在注射吸毒者中的流行病学，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。 公共卫生相关性：该项目的重点是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很重要。