DOT-HARRT for HIV-Infected South African Adults

描述(申请人提供)：联合抗逆转录病毒疗法(ART)时代的早期使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，最近，国际和当地倡议使发展中国家能够获得HAART。来自我之前的工作和其他人的初步数据表明，良好的依从性在资源有限的环境中是可行的，但尚不清楚这些结果是否可以在规模化的ART项目中重现，也不清楚在这种环境下，什么干预措施可能会有效地最大限度地提高依从性。同伴倡导者已经被用来在不同的环境中提高对药物治疗的依从性。为了调查同伴倡导者在南非的潜在效用，我提议进行一项随机试验，300名患者将被分配到PEER-DOT-HAART组或自我给药组，每日两次联合使用Stavudine、Lamivudine和Efavirenz，为期24个月。本研究的具体目的是：1)评价以病毒载量和CD4T细胞计数为指标的Peer-DOT HAART对控制病毒负荷和免疫恢复的影响；2)评估DOT-HAART对治疗依从性的影响；3)测定Peer-DOT与自身使用的HAART药物的耐药比例；4)比较Peer-DOT与自身使用的HAART中新发生或复发的机会性感染的发生率。我的假设是，同级DOT-HAART组的患者将具有高水平的治疗依从性，因此在控制病毒负荷方面更有效，从而限制病毒学失败、耐药性和疾病进展的可能性。这项研究将产生关于提供HAART的替代社区方法的关键数据，HAART可能成为整个撒哈拉以南非洲和发展中国家的护理标准。我的职业发展计划是以研究生培训计划为基础的，其中包括在约翰·霍普金斯大学和开普敦大学的全面课程工作，结构化的指导，以及论文委员会的指导。我的职业规划和研究建议符合我的长期目标，即成为一名有效的独立调查员，并优化撒哈拉以南非洲艾滋病毒感染者的治疗结果。

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 and recently, international and local initiatives have allowed access to HAART in the developing world. Preliminary data from my prior work and others have shown that good adherence is feasible in resource-limited settings, but it is unclear whether these results are reproducible in scaled ART programs and what interventions would likely be effective at maximizing adherence in such settings. Peer advocates have been used to improve adherence with medical therapies in a variety of settings. In order to investigate the potential utility of peer advocates in South Africa, I propose to conduct a randomized trial in which 300 patients will be assigned to either peer-DOT-HAART or self-administration of a twice daily combination of Stavudine, Lamivudine and Efavirenz for 24 months. The specific aims of this study are: 1) to evaluate the impact of peer-DOT HAART on control of viral burden and immune restoration as measured by viral load and CD4 T cell counts; 2) to evaluate the impact of DOT-HAART on treatment adherence; 3) the determination of the proportion of genotypic HAART resistance in the peer-DOT vs. self-administered HAART arms; 4) to compare the incidence of new or recurrent opportunistic infection in the peer-DOT vs. self-administered HAART. My hypothesis is that the patients in the peer-DOT-HAART arm will have high levels of treatment adherence and hence more effective in controlling viral burden, thereby limiting the likelihood of virologic failure, drug resistance, and disease progression. This study will generate critical data on an alternative community-based approach of delivering HAART which may become a standard of care throughout sub-Saharan Africa and the developing world. My career development plan is based on a post-graduate training program, which includes comprehensive coursework at the Johns Hopkins University and University of Cape Town, 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 in sub-Saharan Africa.