Directly observed antiretroviral therapy in drug abusers

描述（由申请人提供）：联合抗逆转录病毒疗法（ART）时代的早期，在工业化国家，与HIV感染相关的发病率和死亡率大幅下降。然而，依从性在优化治疗结果方面的至关重要性很快变得显而易见。我以前的工作表明，注射吸毒者（IDUs）未充分利用ART，并且在使用治疗时存在依从性不足和治疗效果较差的高风险。结核病直接观察治疗（DOT）已被证明是非常有效的，在解决目前面临的问题，在艾滋病毒管理-促进遵守，实现临床成功，并避免耐药性。美沙酮维持治疗是一种有效的阿片类药物成瘾治疗，并提供了一个可行的设置，其中直接管理的抗逆转录病毒治疗（DAART），可提供给艾滋病毒感染者。我建议进行一项前瞻性临床研究，以确定在美沙酮维持诊所提供DAART的有效性。将在DAART参与者和约翰霍普金斯HIV队列研究的匹配参与者中比较临床结局。我的假设是DAART在美沙酮治疗中心将是有效的，与标准治疗相比，它将与改善艾滋病毒治疗结果相关。本项目的具体目的是：1）评估DAART治疗的1年保留率和相关因素，2）评估DAART治疗依从性的时间趋势及其与病毒抑制的相关性，3）比较DAART参与者和接受标准治疗的匹配患者对治疗的病毒学和免疫学应答，比较DAART参与者和接受标准治疗的匹配患者的机会性疾病和死亡的发生率。这个建议直接建立在我之前的工作基础上，为DAART策略的随机多中心试验奠定了基础。我的职业发展计划是基于临床调查研究生培训计划，其中包括在约翰霍普金斯公共卫生学院的综合课程，结构化的指导，并从论文委员会的指导。我的职业规划和研究计划与我的长期目标一致，即成为一名有效的独立研究者，并优化艾滋病毒感染的注射吸毒者的治疗结果。

DESCRIPTION (provided by applicant): The early years of the combination antiretroviral therapy (ART) era have brought about dramatic reductions in the morbidity and mortality associated with HIV infection in industrialized countries. Yet, the critical importance of adherence in optimizing treatment outcomes quickly became evident. My prior work has shown that injection drug users (IDUs) underutilize ART, and are at high risk for inadequate adherence and poorer treatment outcomes when therapy is used. Tuberculosis treatment with directly observed therapy (DOT) has proven remarkably effective in addressing issues currently being confronted in HIV management - promoting adherence, achieving clinical success, and avoiding drug resistance. Methadone maintenance is an effective treatment for opiate addiction and provides a feasible setting in which directly administered antiretroviral therapy (DAART) may be provided to HIV-infected patients. I propose to conduct a prospective clinical study to determine the effectiveness of DAART provided in a methadone maintenance clinic. Clinical outcomes will be compared in DAART participants and matched participants in the Johns Hopkins HIV Cohort Study. My hypothesis is that DAART will be effective in a methadone treatment center and will be associated with improved HIV treatment outcomes compared to standard care. The specific aims of this project are to 1) assess 1-year retention in DAART and associated factors, 2) assess the temporal trend of adherence in DAART and its association with viral suppression, 3) compare virologic and immunologic responses to therapy in DAART participants and matched patients receiving standard care, and 4) compare the incidence of opportunistic diseases and death in DAART participants and matched patients receiving standard care. This proposal builds directly on my prior work and lays the foundation for a randomized, multi-site trial of the DAART strategy. My career development plan is based on the Graduate Training Program in Clinical Investigation, which includes comprehensive coursework at the Johns Hopkins School of Public Health, structured mentoring, and guidance from a thesis committee. My career plan and research proposal are consistent with my long-term goals of becoming an effective independent investigator, and optimizing treatment outcomes in HIV-infected IDUs.