DOT-HARRT for HIV-Infected South African Adults

描述（由申请人提供）：联合抗逆转录病毒疗法（ART）时代的最初几年已经使工业化国家与HIV感染相关的发病率和死亡率大幅下降，最近，国际和地方倡议使发展中国家能够获得HAART。我之前的工作和其他人的初步数据表明，在资源有限的情况下，良好的依从性是可行的，但目前还不清楚这些结果是否在规模化的ART计划中是可重复的，以及在这种情况下，什么样的干预措施可能有效地最大限度地提高依从性。同伴倡导者已被用于在各种环境中提高对药物治疗的依从性。为了研究南非同行倡导者的潜在效用，我建议进行一项随机试验，其中300例患者将被分配到同行DOT-HAART或自我管理的司他夫定，拉米夫定和依法韦仑的每日两次组合24个月。本研究的具体目的是：1）评价对等DOT HAART对病毒负荷控制和免疫恢复的影响，如通过病毒载量和CD 4 T细胞计数测量的; 2）评价DOT-HAART对治疗依从性的影响; 3）确定对等DOT与自我施用HAART组中基因型HAART抗性的比例; 4）比较同伴DOT与自我管理HAART中新发或复发机会性感染的发生率。我的假设是，在同行DOT-HAART臂的患者将有高水平的治疗依从性，因此更有效地控制病毒负荷，从而限制病毒学失败，耐药性和疾病进展的可能性。这项研究将产生关键数据的替代社区为基础的方法提供高效抗逆转录病毒疗法，这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基于研究生培训计划，其中包括在约翰霍普金斯大学和开普敦大学的综合课程，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建议与我的长期目标一致，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.