Impacts of universal access to HIV/AIDS care among HIV+ injection drug users

描述(由申请人提供)：本申请的目的是为长期使用注射药物(IDU)的艾滋病毒感染者寻求新的资金，这些人使用与全面艾滋病毒临床监测有关的注射药物，以检查个人、社会、政策、经济和身体暴露对艾滋病毒治疗结果的影响。我们试图分析这些背景决定因素，包括监禁、无家可归和涉及性交易，在个人和社区层面上对艾滋病毒RNA血浆病毒载量的影响。我们将用基于分子遗传学和地理信息系统(GIS)的方法加强我们正在进行的流行病学和临床研究活动，以模拟这些暴露对社区水平血浆病毒载量、艾滋病毒发病率和抗逆转录病毒耐药性产生的影响。鉴于国际社会对艾滋病毒“风险环境”的日益关注，这是一个模拟外源性和内源性特征对艾滋病毒感染风险的影响的概念框架，我们将利用这一结构在艾滋病毒治疗结果分析中整合来自个人和社区层面的数据。这项建议是在国际社会广泛共识需要紧急应对注射吸毒者艾滋病毒相关发病率和死亡率持续上升的情况下提出的。来自数学建模、观察性队列和临床试验的新证据表明，个人内和社区一级的艾滋病毒RNA病毒载量与艾滋病毒在个人之间传播的风险之间存在密切联系，从而导致高效抗逆转录病毒疗法(HAART)覆盖率较高的人群的感染率较低。这一观察结果导致了新的艾滋病毒预防努力，以寻找弱势群体成员，对他们进行艾滋病毒感染检测，并让他们参与医疗保健，包括艾滋病毒感染的治疗，以减少艾滋病毒相关的发病率和死亡率，并降低艾滋病毒血清转换的发生率。我们建议的研究将在全省范围内开展“寻求、测试和治疗”活动。鉴于迄今为止建立的研究基础设施以及我们评估获得和遵守HAART的障碍的记录，我们处于独特的有利地位，可以前瞻性地评估有关预防活动对社区水平血浆病毒载量、HAART耐药性和艾滋病毒发病率的影响的第二代治疗问题。在这方面，将治疗作为预防进行评估是2012财年国家卫生研究院艾滋病毒相关研究跨国家卫生组织计划的一项紧迫优先事项。除了“寻找、测试和治疗”活动外，我们在加拿大温哥华的研究环境非常适合我们的研究目标。全民医疗体系免费提供包括HAART在内的所有医疗服务。保密的记录链接可以准确地实现所有关键措施，包括卫生服务利用率和艾滋病毒临床结果。这项申请提出了一项严谨和创新的研究计划，将整合流行病学、地理学和系统发生学方法，为应对注射吸毒者中艾滋病毒传播和发病机制的努力提供关键信息。 公共卫生相关性：注射吸毒者中艾滋病毒高水平感染是全球公共卫生紧急情况。作为回应，我们建议更新我们正在进行的艾滋病毒阳性吸毒者研究，以评估艾滋病毒治疗对抗逆转录病毒药物模式的影响。 加拿大温哥华艾滋病毒的耐药性和传播模式。

DESCRIPTION (provided by applicant): The purpose of this application is to seek renewed funding for a long-running prospective cohort of HIV- infected individuals who use injection drugs (IDU) linked to comprehensive HIV clinical monitoring to examine the impacts of individual, social, policy, economic, and physical exposures on HIV treatment outcomes. We seek to analyse the effects of these contextual determinants, including incarceration, homelessness, and involvement in the sex trade, on HIV RNA plasma viral load at both the individual and community levels. We will augment our ongoing epidemiologic and clinical research activities with molecular genetics and geographic information systems (GIS) based methods to model the effect of these exposures on community-level plasma viral load, HIV incidence, and the generation of antiretroviral drug resistance. In recognition of the increasing international attention to the HIV "risk environment," a conceptual framework modeling the effect of exogenous and endogenous characteristics on the risk of HIV infection, we will employ this structure to integrate data from individual and community levels in analyses of HIV treatment outcomes. This proposal comes at a time of broad international consensus on the need to respond urgently to persistently elevated levels of HIV-related morbidity and mortality among IDU. Emerging evidence from mathematical modeling, observational cohorts and clinical trials has revealed the close link between the HIV RNA viral load within individuals and at the community level and the risk of HIV transmission between individuals, resulting in lower rates of infection in populations with higher levels of coverage of highly active antiretroviral therapy (HAART.) This observation has led to renewed HIV prevention efforts to seek out members of vulnerable populations, test them for HIV infection, and engage them in healthcare, including treatment for HIV infection, in order to reduce HIV-related morbidity and mortality and lower the incidence of HIV seroconversion. Our proposed study will be conducted during a province-wide "Seek, Test, and Treat" campaign. Given the study infrastructure established to date and our track record evaluating barriers to HAART access and adherence, we are uniquely well placed to prospectively assess second-generation questions regarding the treatment as prevention campaign's impacts on community-level plasma viral loads, HAART resistance, and HIV incidence. In this regard, evaluations of treatment as prevention are an urgent priority in the FY 2012 Trans-NIH Plan for HIV-Related Research. In addition to the "Seek, Test, and Treat" campaign, our study setting of Vancouver, Canada, is ideally suited to our study aims. The universal healthcare system provides all medical care, including HAART, free of charge. Confidential record linkages allow the accurate attainment of all key measures, including health service utilization and HIV clinical outcomes. This application proposes a program of rigorous and innovative study that will marshal epidemiologic, geographic, and phylogenetic approaches to critically inform efforts to respond to HIV transmission and pathogenesis among IDU. PUBLIC HEALTH RELEVANCE: High levels of HIV infection among people who use injection drugs is a global public health emergency. In response, we propose to renew our ongoing study of HIV-positive drug users to assess the effect of HIV treatment on patterns of antiretroviral drug resistance and patterns of HIV transmission in Vancouver, Canada.