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

优化儿童艾滋病毒/结核病联合治疗方案的药代动力学和规划评估

• 批准号: 9140789
• 负责人: Holly Elizabeth Rawizza
• 金额: $ 18.52万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9140789
• 关键词: 12 year old; 3 year old; AIDS prevention; Address; Adult; Age; Anti-Retroviral Agents; Caring; Child; Childhood; Clinical; Country; Data; Data Reporting; Databases; Drug Interactions; Drug Kinetics; Enrollment; Epidemic; Evaluation; Funding; Future; Goals; Guidelines; HIV; Home environment; IMPAACT; Improve Access; K-Series Research Career Programs; Knowledge; Laboratories; Life; Literature; Lopinavir/Ritonavir; Monitor; Mono-S; Nigeria; Nucleosides; Outcome; Patients; Pharmacotherapy; Population; Process; Protease Inhibitor; Public Health; Recommendation; Regimen; Relapse; Research; Research Design; Research Priority; Resources; Rifabutin; Rifampin; Rifamycins; Safety; Services; Site; Statistical Methods; Time; Translating; Treatment Failure; Treatment Protocols; Treatment outcome; Tuberculosis; Work; World Health Organization; antiretroviral therapy; base; clinical care; co-infection; cohort; design; experience; follow-up; improved; improved outcome; mortality; novel; pediatric human immunodeficiency virus; pediatric patients; programs; prospective; public health relevance; screening; skills; treatment program; treatment strategy; tuberculosis treatment

 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.

 描述（由申请人提供）：全球艾滋病毒和结核病（TB）流行的汇合是全球公共卫生面临的最紧迫挑战之一。尽管获得抗逆转录病毒疗法的机会有所改善，但结核病仍然是艾滋病毒感染儿童的主要杀手。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（世卫组织）已将评价儿童新的治疗选择指定为研究重点。为了解决这一问题，我们将结合联合收割机程序和药代动力学（PK）分析，以严格评估当前和未来有希望的治疗方案。我们将通过检查参加哈佛/尼日利亚艾滋病预防倡议（APIN）计划的5500多名儿科患者的10年治疗数据来评估目前的儿科HIV/TB联合治疗方案，以确定HIV/TB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。我们还将在合并感染儿童中评估两种新型治疗策略的药代动力学、安全性和疗效：（1）基于利福布丁的TB治疗联合基于LPV/r的ART;（2）基于度鲁特韦的ART联合基于利福平的TB治疗，以IMPAACT P1093研究的新结果为基础。项目结果和PK分析的结合将为推进儿童HIV/TB合并感染的治疗提供关键数据。自2004年以来，哈佛/APIN PEPFAR计划为尼日利亚的15万多人提供了艾滋病毒护理服务，其中包括5500多名儿童。参加该方案的儿童可获得免费的临床护理、抗逆转录病毒治疗、结核病筛查和实验室监测。这项研究将建立在这个完善的艾滋病毒治疗计划，以检查关键问题的努力，以改善儿科艾滋病毒/结核病的结果。尼日利亚是艾滋病毒感染儿童最多的国家，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和进行PK研究以评估两种新的联合治疗方案，我们将获得必要的知识，这些知识可能转化为治疗建议的改变，并开始遏制结核病的毁灭性死亡。