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: 10422433
• 负责人: Holly Elizabeth Rawizza
• 金额: $ 5.9万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-03 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10422433
• 关键词: Acquired Immunodeficiency Syndrome; Address; Child; Childhood; Country; Data; Drug Kinetics; Enrollment; Epidemic; Evaluation; Future; Goals; HIV; HIV/TB; Home; Improve Access; International Maternal Pediatric Adolescent AIDS Clinical Trials; Knowledge; Laboratories; Monitor; Nigeria; Outcome; Prevention; Public Health; Recommendation; Regimen; Research; Research Priority; Rifabutin; Rifampin; Safety; Translating; Treatment Failure; Treatment Protocols; Treatment outcome; Tuberculosis; World Health Organization; antiretroviral therapy; base; care systems; clinical care; co-infection; improved; mortality; novel; optimal treatments; pediatric human immunodeficiency virus; pediatric patients; programs; prospective; screening; treatment guidelines; treatment program; treatment strategy; tuberculosis treatment

PROJECT SUMMARY/ABSTRACT 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 examinig 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 build 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.

项目总结/摘要 全球艾滋病毒和结核病（TB）流行病的汇合是全球最严重的疾病之一。 全球公共卫生面临的紧迫挑战。尽管获得抗逆转录病毒疗法的机会有所改善， 结核病仍然是感染艾滋病毒儿童的主要杀手。此外，治疗儿童的任务- 由于缺乏最佳治疗方案，艾滋病毒和结核病感染者仍然特别具有挑战性。 因此，世界卫生组织（世卫组织）已指定评价较新的治疗方法， 儿童的选择是研究的优先事项。为了解决这个问题，我们将把联合收割机和 药代动力学（PK）分析，以批判性地评价当前和有希望的未来治疗 养生法我们将通过检查10年的儿童艾滋病毒/结核病联合治疗方案， 年参加哈佛/艾滋病预防倡议的5500多名儿科患者的治疗数据， 尼日利亚（APIN）项目，以确定艾滋病毒/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。我们还将评估药代动力学， 两种新的治疗策略在合并感染儿童中的安全性和有效性：（1）以利福布丁为基础的 TB治疗联合基于LPV/r的ART;和（2）基于度鲁特韦的ART联合 基于IMPAACT P1093研究的新结果。这 方案成果和PK分析的结合将提供关键数据， 治疗儿童HIV/TB合并感染。 哈佛/APIN PEPFAR计划为15万多人提供了艾滋病毒护理服务， 尼日利亚，自2004年以来，包括5 500多名儿童。参加该计划的儿童将获得免费的临床 护理、抗逆转录病毒治疗、结核病筛查和实验室监测。本研究将以此为基础 一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/结核病成果。尼日利亚是艾滋病毒感染儿童最多的国家， 仅2012年就有6万儿童新感染艾滋病毒。通过批判性地评估我们目前的努力， 进行PK研究以评价两种新型联合治疗方案，我们将获得必要的知识 这可能会转化为治疗建议的改变，并开始遏制结核病的破坏性 通行费