INCIDENCE OF HIV INFECTION IN A COHORT OF IV DRUG USERS

描述（由申请人提供）：在这一竞争更新中，我们建议在马里兰州巴尔的摩参加艾滋病与静脉注射经验（ALIVE-II）研究的HIV未感染注射吸毒者（IDUs）中继续进行为期25年的HIV风险流行病学调查。该研究提供了对HIV感染动态和风险行为的关键见解，同时作为HIV阳性IDUs平行队列（DA04334, ALIVE-I）的对照组。在过去的资助周期中，我们的研究团队取得了很高的成果（发表了112篇论文和77次主要演讲），在未来五年内，我们将继续开展前沿和创新的广泛基础研究，同时为与HIV和HCV感染相关的临床和发病机制研究提供资源。在本提案中，我们提出了与丙型肝炎病毒（HCV）相关的重点工作，这代表了idu在未来十年将面临的主要挑战。在IDU人群中，丙型肝炎病毒的患病率为50-90%，预计在未来十年中，丙型肝炎病毒感染的发病率和死亡率将急剧增加。根据从艾滋病毒中吸取的经验教训，我们侧重于收集信息，以评估当前HCV“检测和治疗”行动在人群层面的有效性，并为制定针对HCV检测、与护理、治疗和治疗作为预防（HCV- tasp）的新干预措施提供见解。我们的具体目标是：1)描述注射吸毒者对丙型肝炎病毒的持续治疗及其随着时间的推移随着抗病毒治疗的日益有效的演变；2)评估巴尔的摩注射吸毒者丙型肝炎治疗的人群水平有效性；3)建立HCV治疗动态的数学模型，以评估不同干预策略的潜在影响和成本效益；4)继续作为非艾滋病结果纵向调查的HIV阴性对照组和独立资助的相关研究平台。为了实现这些目标，我们将继续对艾滋病毒阴性注射吸毒者（约1000人）进行半年一次的随访，并将在拟议的资助期内进行两次招聘。2013-2014年和2016-2017年新增招聘；每个时间点将通过街道外展累计500名参与者。ALIVE-II队列的独特之处在于，它包括以社区为基础的IDU人口，男女都有，非洲裔美国人和获得适当医疗服务有限的人具有重要代表性；在关于艾滋病毒感染风险人群的研究中，这些人群的代表性不足。我们与live -i合作，这是一个平行的艾滋病毒感染静脉注射者队列，利用相同的方案、设施和工作人员，没有财政重叠。考虑到所提出方法的科学严谨性、现有的基础设施、经验丰富的研究人员和nih资助的多项辅助研究，我们期待持续的成功和实质性的科学贡献。

DESCRIPTION (provided by applicant): In this competing renewal, we propose to continue a 25-year investigation of the epidemiology of HIV risk among HIV-uninfected injection drug users (IDUs) enrolled in the AIDS Linked to the IntraVenous Experience (ALIVE-II) Study in Baltimore, MD. This study has provided critical insight into the dynamics of HIV infection and risk behavior while serving as a comparison group to a parallel cohort of HIV positive IDUs (DA04334, ALIVE-I). Our investigative team has been highly productive during the past funding cycle (112 publications & 77 major presentations) and, over the next five years, we will continue cutting-edge and innovative broad- based investigations, while serving as a resource for clinical and pathogenesis studies related to HIV and HCV infection. In this proposal, we present a focused effort related to hepatitis C virus (HCV), which represents the major challenge that IDUs will face over the next decade. HCV prevalence ranges from 50-90% in IDU populations and morbidity and mortality secondary to HCV infection is expected to dramatically increase over the next decade. Building on lessons learned from HIV, we focus on collecting information to evaluate the population-level effectiveness of current HCV 'Test-and-Treat' initiatives and provide insight to the development of new interventions to target HCV testing, linkage to care, treatment and Treatment as Prevention (HCV-TasP). Our Specific Aims are to: 1) Characterize the continuum of care for HCV among IDUs and its evolution over time with increasingly efficacious antiviral therapy; 2) Assess population-level effectiveness of hepatitis C treatment among IDUs in Baltimore; 3) Develop a mathematical model of HCV treatment dynamics to assess the potential impact and cost-effectiveness of different intervention strategies; and 4) continue to serve as an HIV negative comparison group for longitudinal investigation of non-AIDS outcomes and a platform for independently funded related studies. To achieve these aims, we will continue follow-up of a cohort of HIV negative IDUs (~1000) with semiannual visits and will open recruitment twice over the proposed funding period. New recruitment will occur in 2013-2014 and 2016-2017; 500 participants at each time point will be accrued via street outreach. The ALIVE-II cohort is unique in that it comprises a community- based IDU population of both genders with significant representation of African-Americans and those with limited access to appropriate medical care; these populations have been underrepresented in research on persons at risk for HIV infection. We collaborate with ALIVE-I, a parallel cohort of HIV-infected IDUs that capitalizes on the same protocol, facilities and staff with no fiscal overlap. Given the scientific rigor of the proposed methods, existing infrastructure, experienced investigators and multiple NIH-funded ancillary studies, we anticipate continued success and substantial scientific contribution.