Protection from HIV Infection in Intravenous Drug Users

描述（申请人提供）：博士。Jay Levy和Don Des Jarlais进行了一项试点研究，研究暴露于艾滋病毒的注射吸毒者（IDUs）中有相当大比例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，保护了通过非静脉传播途径接触艾滋病毒的其他个体（见下文）。在初步研究中，30个未感染的idu中有7个（23%）表现出先天的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。这项建议的目的是对这一关于注射药物的重要观察进行深入研究。包括进一步评估注射吸毒者高危行为与CNAR的关系，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细胞的免疫活动以及免疫激活作为影响感染抗性的可能因素。本课题的具体研究目的如下：1。确定CD8+细胞非细胞毒性抗病毒反应（CNAR）在最近（过去一年）通过注射危险行为暴露于HIV的可能性高和通过性危险行为暴露于HIV的可能性低的HIV血清阴性注射吸毒者中的流行程度。我们将检验这一假设，即近期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比近期注射风险低和性行为暴露于艾滋病毒的风险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的数量和免疫激活是否与HIV血清阴性IDUs感染的潜在保护有关。这些目标将通过从160名受试者获得额外的血液样本来实现，这些受试者将被纳入风险因素研究：80名注射吸毒者，最近暴露于艾滋病毒的注射风险高，性风险低，40名注射吸毒者，注射风险低，性风险低，20名艾滋病毒阴性非注射吸毒者，20名艾滋病毒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以防止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大大有助于了解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重要信息。

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.