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.

项目摘要/摘要 全球艾滋病毒和结核病（TB）发作的融合代表了最多的事件之一 全球公共卫生面临的紧急挑战。尽管改善了抗逆转录病毒疗法（ART）的机会，但 结核病仍然是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，感染艾滋病毒和结核病仍然特别具有挑战性。 结果，世界卫生组织（WHO）指定了对新治疗的评估 儿童的选择优先。为了解决这个问题，我们将结合程序化和 药代动力学（PK）分析以批判性评估当前和有希望的未来治疗 方案。我们将通过考试评估当前的小儿艾滋病毒/结核病共同治疗选项10年 来自哈佛/艾滋病预防计划的5500多名儿科患者的治疗数据 尼日利亚（APIN）计划，以确定HIV/TB治疗失败和/或死亡率的预测因素， 特别关注艺术时机和方案选择。我们还将评估药代动力学， 共同感染的儿童两种新型治疗策略的安全性和有效性：（1）基于利法布丁的儿童 结核病治疗与基于LPV/R的ART结合； （2）基于Dolutegravir并发的艺术 基于Rifampin的结核病治疗，基于Incacact P1093研究的新出现。这 编程结果和PK分析的组合将提供关键数据以促进 小儿HIV/TB共感染的治疗。 哈佛大学/Apin Pepfar计划已为超过15万人提供了艾滋病毒护理服务 自2004年以来，尼日利亚包括超过5500名儿童。参加此计划的儿童获得免费临床 护理，抗逆转录病毒疗法，结核病筛查和实验室监测。这项研究将基于此 良好的艾滋病毒治疗计划，以研究为改善小儿而努力至关重要的问题 艾滋病毒/结核病结果。尼日利亚是艾滋病毒感染艾滋病毒的儿童的家 仅在2012年，有60,0000名儿童刚刚感染了艾滋病毒。通过批判性评估我们当前的努力和 进行PK研究以评估两种新型的共同处理方案，我们将获得基本知识 这可能转化为治疗建议的变化，并开始遏制TB的破坏性 收费。