INCIDENCE OF HIV INFECTION IN A COHORT OF IV DRUG USERS

描述(由申请人提供)：在这项竞争性的更新中，我们建议继续一项为期25年的研究，调查在马里兰州巴尔的摩进行的静脉注射体验(Alive-II)研究中登记的艾滋病患者中未感染艾滋病毒的注射吸毒者(IDU)中的艾滋病毒风险。这项研究为艾滋病毒感染和危险行为的动态提供了重要的洞察力，同时作为与艾滋病毒阳性注射人群(DA04334，Alive-I)平行队列的对照组。我们的调查团队在过去的资金周期中卓有成效(112篇出版物和77篇主要报告)，在接下来的五年里，我们将继续进行前沿和创新的广泛研究，同时成为与艾滋病毒和丙型肝炎病毒感染有关的临床和发病机制研究的资源。在这项提案中，我们提出了与丙型肝炎病毒(丙型肝炎病毒)相关的重点工作，这代表了注射吸毒者在未来十年将面临的主要挑战。在注射吸毒者中，丙型肝炎病毒的流行率从50%到90%不等，预计在接下来的十年中，丙型肝炎病毒感染继发的发病率和死亡率将大幅增加。在从艾滋病毒中吸取教训的基础上，我们专注于收集信息，以评估当前丙型肝炎病毒“检测和治疗”举措在人群层面的有效性，并为针对丙型肝炎病毒检测的新干预措施的开发提供洞察，将其与护理、治疗和治疗作为预防(丙型肝炎病毒-TasP)相联系。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护理及其随着抗病毒治疗日益有效而随时间的演变；2)评估巴尔的摩注射吸毒者中丙型肝炎治疗的人群水平的有效性；3)建立丙型肝炎病毒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；以及4)继续作为艾滋病毒阴性对照小组，对非艾滋病结果进行纵向调查，并成为独立资助相关研究的平台。为了实现这些目标，我们将继续对一批艾滋病毒阴性的注射吸毒者(约1000人)进行半年一次的访问，并将在拟议的资助期内两次公开招募。2013-2014年和2016-2017年将进行新的征聘；每个时间点将通过街头外联累积500名参与者。Alive-II人群的独特之处在于，它包括以社区为基础的注射吸毒者人群，其中非洲裔美国人占很大比例，获得适当医疗服务的机会有限；在关于艾滋病毒感染风险人群的研究中，这些人群的比例偏低。我们与Alive-I合作，这是一个平行的艾滋病毒感染注射人群队列，利用相同的方案、设施和工作人员，没有财政重叠。考虑到拟议方法的科学严谨性、现有的基础设施、经验丰富的研究人员和多项由美国国立卫生研究院资助的辅助研究，我们预计将继续取得成功并做出重大的科学贡献。

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.