Directly observed antiretroviral therapy in drug abusers

描述(申请人提供)：在联合抗逆转录病毒疗法(ART)时代的早期，工业化国家与艾滋病毒感染相关的发病率和死亡率大幅下降。然而，坚持治疗在优化治疗结果方面的关键重要性很快就变得明显起来。我以前的工作表明，注射吸毒者(IDU)没有充分利用抗逆转录病毒治疗，在使用治疗时，他们面临依从性不足和治疗结果较差的高风险。用直接观察疗法(DOT)治疗结核病已被证明在解决艾滋病毒管理中目前面临的问题方面非常有效--促进坚持、取得临床成功和避免耐药性。维持美沙酮是治疗阿片成瘾的有效方法，并为艾滋病毒感染者提供了直接实施抗逆转录病毒疗法(DAART)的可行环境。我建议进行一项前瞻性临床研究，以确定美沙酮维持治疗诊所提供的DAART的有效性。在约翰霍普金斯大学HIV队列研究中，将比较DAART参与者和匹配参与者的临床结果。我的假设是，与标准治疗相比，DAART在美沙酮治疗中心将有效，并将与改善艾滋病毒治疗结果相关。该项目的具体目标是：1)评估在DAART中保留1年的情况和相关因素；2)评估DAART中坚持治疗的时间趋势及其与病毒抑制的关系；3)比较DAART参与者和接受标准护理的匹配患者对治疗的病毒学和免疫学反应；4)比较DAART参与者和接受标准护理的匹配患者的机会性疾病和死亡的发生率。这项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，其中包括约翰·霍普金斯公共卫生学院的全面课程工作、结构化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调查者，并优化感染艾滋病毒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.