Directly observed antiretroviral therapy in drug abusers

描述（由申请人提供）：在早期的抗逆转录病毒联合疗法（ART）时代，工业化国家与艾滋病毒感染相关的发病率和死亡率显著降低。然而，依从性在优化治疗结果中的关键重要性很快变得明显。我之前的工作表明，注射吸毒者（IDUs）没有充分利用抗逆转录病毒治疗，并且在使用治疗时，存在依从性不足和治疗结果较差的高风险。事实证明，采用直接观察疗法（DOT）治疗结核病在解决当前艾滋病毒管理面临的问题方面非常有效——促进坚持治疗、取得临床成功和避免耐药性。美沙酮维持是一种有效的阿片成瘾治疗方法，并为向艾滋病毒感染患者提供直接给予抗逆转录病毒治疗（DAART）提供了可行的环境。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。临床结果将比较DAART参与者和约翰霍普金斯HIV队列研究中匹配的参与者。我的假设是，与标准治疗相比，DAART在美沙酮治疗中心将是有效的，并且与改善的艾滋病毒治疗结果有关。该项目的具体目的是：1)评估DAART的1年保留率及相关因素；2)评估DAART依从性的时间趋势及其与病毒抑制的关系；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反应；4)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发生率。该建议直接建立在我之前的工作基础上，并为DAART策略的随机、多地点试验奠定了基础。我的职业发展计划是基于临床调查研究生培训计划，包括在约翰霍普金斯大学公共卫生学院的综合课程，结构化的指导和论文委员会的指导。我的职业规划和研究计划与我的长期目标是一致的，即成为一名有效的独立研究者，并优化hiv感染idu的治疗效果。

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.