HIV Treatment Failure and Drug Resistance in Western Kenyan Children

肯尼亚西部儿童的艾滋病毒治疗失败和耐药性

• 批准号: 9925893
• 负责人: Rami Kantor
• 金额: $ 72万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-06 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9925893
• 关键词: 14 year old; Academic Medical Centers; Adherence; Adolescence; Adolescent; Adult; Affect; Africa South of the Sahara; African; American; Antiretroviral resistance; Birth; Blood; Blood Banks; Blood specimen; Caring; Cessation of life; Child; Childhood; Chronic Disease; Clinical; Clinical Data; Cohort Studies; Collection; Comprehensive Health Care; Data; Development; Disease Management; Dose; Drug resistance; Electronic Health Record; Enrollment; Evolution; Face; Failure; Funding; Goals; Guidelines; HIV; HIV Infections; HIV drug resistance; Hour; Immunologics; Individual; Infrastructure; Interruption; Intervention; Investigation; Kenya; Laboratories; Lead; Literature; Long-Term Care; Longitudinal Studies; Maintenance; Medical Records; Methods; Modeling; Monitor; Outcome; Participant; Patient Care; Patients; Pattern; Pediatric cohort; Pharmaceutical Preparations; Pharmacy facility; Prevalence; Public Health; Recommendation; Regimen; Research; Resistance; Resistance development; Resources; Retrospective cohort study; Risk; Sampling; Shapes; Specimen; System; Technology; Testing; Time; Treatment Failure; United States National Institutes of Health; Viral; Virus; Weight; Work; antiretroviral therapy; base; care outcomes; clinical care; clinical research site; cohort; drug development; effective therapy; electronic data; follow-up; health care availability; improved; innovation; medication nonadherence; novel; pediatric human immunodeficiency virus; pediatric human immunodeficiency virus infection; pediatric patients; perinatal HIV; prospective; public health relevance; resistance mutation; success; therapy development; treatment guidelines; virology

 DESCRIPTION (provided by applicant): Resistance to antiretroviral therapy (ART) poses significant barriers to effective treatment of HIV infection and optimal long-term clinical care outcomes; however, there are few longitudinal data on rates of and factors associated with viral failure and resistance development in children, particularly in sub-Saharan Africa, where over 90% of HIV-infected children live. The long-term goal of our research team is to provide new evidence to improve the clinical disease management of HIV-infected children and adolescents in resource-limited settings. The purpose of this proposal is to longitudinally investigate treatment failure, drug resistance and associated factors among a previously established, carefully characterized cohort of 685 HIV-infected children in western Kenya. This work will be conducted within a long-standing US-Kenya partnership, the Academic Model Providing Access to Healthcare (AMPATH), which currently cares for over 70,000 adult and pediatric HIV- infected individuals at 65 clinical sites in Kenya. We will utilize the excellent AMPATH infrastructure, as well as a previous NIH-funded study that established this cohort of children (Vreeman: 1K23MH087225), to provide novel and significant data on the development of failure and resistance over five years. The Specific Aims of the proposal are: Aim 1: Determine the prevalence of viral failure and examine drug resistance mutation patterns among a retrospective study cohort of 685 perinatally HIV-infected Kenyan children on 1st-line ART. Aim 2: Investigate associations between specific adherence patterns, ART drug levels and other demographic and clinical factors, with viral failure and drug resistance; Aim 3: Study long-term immunologic, virologic and drug resistance outcomes and their associations in prospectively re-enrolled study participants; and Aim 4: Enhance analyses of viral failure, drug resistance accumulation and associated demographic and clinical factors by examining the longitudinal banked samples available for a subset of the study cohort (n=327). To achieve these aims, we will use previously collected, banked blood specimens of the study cohort (collected between May 2010-October 2013), along with detailed adherence data from electronic dose monitoring and drug concentrations; re-enroll as many of the study cohort as possible for an additional blood draw; assess long-term treatment failure and drug resistance using novel resistance testing technologies; use the established AMPATH Medical Records System to obtain all clinical and pharmacy data for each child from enrollment in AMPATH to present to examine longitudinal associations with failure and resistance; and conduct prospective electronic dose monitoring of current adherence for a subset of the cohort. This research will significantly impact understanding of longitudinal failure and resistance development and which factors influence their development. This proposal is unique because we propose: (1) longitudinal investigation of failure and resistance; (2) innovative approaches to drug resistance testing; and (3) detailed investigation of adherence, drug concentration and other clinical data, to impact pediatric HIV care in resource limited settings.

 描述（由适用提供）：对抗逆转录病毒疗法（ART）的耐药性具有有效治疗HIV感染和最佳长期临床护理结果的重大障碍；但是，几乎没有关于儿童病毒衰竭和耐药性发展的纵向数据，特别是在撒哈拉以南非洲，超过90％的HIV感染儿童居住。我们的研究团队的长期目标是提供新的证据，以改善在资源有限的环境中，在资源有限的环境中改善艾滋病毒感染的儿童和青少年的临床疾病管理。该提案的目的是纵向研究肯尼亚西部685名HIV感染儿童的先前建立，精心表征的人群中的治疗失败，耐药性和相关因素。这项工作将在长期以来的US-Kenya合作伙伴关系中进行，该合作伙伴关系提供了医疗保健（AMPATH）的学术模型，目前在肯尼亚的65个临床场所关心70,000多名成人和儿科感染的HIV感染者。我们将利用出色的Ampath基础设施以及以前的NIH资助研究，该研究建立了这一群体（Vreeman：1K23MH087225），以提供有关五年来失败和抵抗力发展的新颖和重要数据。该提案的具体目的是：目标1：确定一项一线艺术对685个围绕艾滋病毒感染的肯尼亚儿童的回顾性研究队列中病毒衰竭和耐药性突变模式的普遍性。目标2：研究特定的依从性模式，ART药物水平与其他人口统计学和临床​​因素之间的关联以及病毒衰竭和耐药性； AIM 3：研究长期免疫，病毒和耐药性结果及其在前瞻性重新注册研究参与者中的关联；和目标4：通过检查可用于研究队列的一部分的纵向银行样品，增强了病毒衰竭，耐药性积累以及相关的人口统计和临床因素的分析（n = 327）。为了实现这些目标，我们将使用先前收集的研究队列的库存血液标本（2010年5月至2013年10月之间收集），以及来自电子剂量监测和药物浓度的详细依从性数据；尽可能多的研究队列以额外的抽血来重新注册；使用新型耐药性测试技术评估长期治疗失败和耐药性；使用已建立的AMPATH病历系统获取每个儿童的所有临床和药学数据，从Ampath的入学到出现到检查失败和抵抗力的纵向关联；并对同类子集的当前依从性进行前瞻性电子剂量监测。这项研究将显着影响对纵向失败和抵抗发展的理解，以及哪些因素影响其发展。该提议是独一无二的，因为我们提出：（1）失败和抵抗的纵向投资； （2）耐药性测试的创新方法； （3）对依从性，药物浓度和其他临床数据的详细研究，以影响资源限制设置中的小儿HIV护理。