Pharmacokinetic and Programmatic Evaluations to Optimize HIV/TB Co-Treatment Regimens in Children

 描述（由申请人提供）：全球艾滋病毒和结核病（TB）流行的融合是全球公共卫生面临的最紧迫的挑战之一。尽管抗逆转录病毒治疗 (ART) 的普及程度有所提高，但结核病仍然是感染艾滋病毒儿童的主要杀手。此外，由于缺乏最佳治疗方案，治疗同时感染艾滋病毒和结核病的儿童的任务仍然特别具有挑战性。因此，世界卫生组织 (WHO) 已将评估儿童新治疗方案列为研究重点。为了解决这个问题，我们将结合程序分析和药代动力学（PK）分析来严格评估当前和有前途的未来治疗方案。我们将通过检查参加尼日利亚哈佛/艾滋病预防计划 (APIN) 项目的 5500 多名儿科患者 10 年的治疗数据来评估当前的儿科 HIV/结核病联合治疗方案，以确定 HIV/结核病治疗失败和/或死亡率的预测因素，特别关注 ART 时机和方案选择。我们还将评估两种新型治疗策略在合并感染儿童中的药代动力学、安全性和有效性：（1）基于利福布丁的结核病治疗联合基于LPV/r的ART； (2) 以多替拉韦为基础的 ART 与同时以利福平为基础的结核病治疗，以 IMPAACT P1093 研究的新结果为基础。规划结果和 PK 分析的结合将为推进儿科 HIV/TB 合并感染的治疗提供关键数据。自 2004 年以来，哈佛/APIN PEPFAR 计划已为尼日利亚超过 150,000 人提供艾滋病毒护理服务，其中包括超过 5500 名儿童。参加该计划的儿童可以获得免费临床护理、抗逆转录病毒治疗、结核病筛查和实验室监测。这项研究将以这一完善的艾滋病毒治疗计划为基础，研究对于改善儿童艾滋病毒/结核病结果至关重要的问题。尼日利亚是感染艾滋病毒的儿童数量最多的国家，仅 2012 年就有 6 万名儿童新感染艾滋病毒。通过严格评估我们目前的努力并进行 PK 研究来评估两种新型联合治疗方案，我们将获得必要的知识，这些知识可能会转化为治疗建议的改变，并开始遏制结核病的毁灭性损失。

 DESCRIPTION (provided by applicant): The convergence of the global HIV and tuberculosis (TB) epidemics represents one of the most urgent challenges facing global public health. Despite improved access to antiretroviral therapy (ART), TB remains the leading killer of children with HIV. Furthermore, the task of treating children co- infected with HIV and TB remains particularly challenging due to lack of optimal treatment regimens. As a result, the World Health Organization (WHO) has designated the evaluation of newer treatment options for children a research priority. To address this issue, we will combine programmatic and pharmacokinetic (PK) analyses to critically evaluate both current and promising future treatment regimens. We will assess current pediatric HIV/TB co-treatment options by examining 10 years of treatment data from over 5500 pediatric patients enrolled in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) program to identify predictors of HIV/TB treatment failure and/or mortality, with a particular focus on ART timing and regimen selection. We will also evaluate the pharmacokinetics, safety, and efficacy of two novel treatment strategies among co-infected children: (1) rifabutin-based TB treatment in combination with LPV/r-based ART; and, (2) dolutegravir-based ART with concurrent rifampin-based TB treatment, building upon emerging results from the IMPAACT P1093 study. This combination of programmatic outcomes and PK analyses will provide critical data to advance the treatment of pediatric HIV/TB co-infection. The Harvard/APIN PEPFAR program has supported HIV care services for over 150,000 people in Nigeria including over 5500 children since 2004. Children enrolled in this program receive free clinical care, antiretroviral therapy, TB screening, and laboratory monitoring. This study will buid upon this well-established HIV treatment program to examine issues critical for efforts to improve pediatric HIV/TB outcomes. Nigeria is home to more children living with HIV than any other country, with 60,0000 children newly infected with HIV in 2012 alone. By critically evaluating our current efforts and performing PK studies to evaluate two novel co-treatment regimens, we will gain essential knowledge that may translate into a change in treatment recommendations and begin to curb TB's devastating toll.