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.

 抗逆转录病毒疗法（ART）耐药性对HIV感染的有效治疗和最佳长期临床护理结果构成重大障碍;然而，关于儿童病毒治疗失败和耐药性发展的比率和相关因素的纵向数据很少，特别是在撒哈拉以南非洲，那里有超过90%的HIV感染儿童。我们研究小组的长期目标是提供新的证据，以改善在资源有限的环境中感染艾滋病毒的儿童和青少年的临床疾病管理。本建议的目的是纵向调查治疗失败，耐药性和相关因素之间的一个先前建立的，仔细表征的队列685艾滋病毒感染的儿童在肯尼亚西部。这项工作将在长期的美国-肯尼亚合作伙伴关系中进行，即提供医疗保健的学术模式（AMPATH），该模式目前在肯尼亚的65个临床站点照顾超过70，000名成人和儿童艾滋病毒感染者。我们将利用优秀的AMPATH基础设施，以及之前由NIH资助的建立该儿童队列的研究（Vreeman：1 K23 MH 087225），提供关于五年内失败和耐药性发展的新的重要数据。该提案的具体目标是：目标1：确定病毒失败的患病率，并检查685名接受一线抗逆转录病毒治疗的围产期感染艾滋病毒的肯尼亚儿童的回顾性研究队列中的耐药性突变模式。目标2：调查特定依从性模式、抗逆转录病毒治疗药物水平和其他人口统计学和临床因素与病毒失败和耐药性之间的关联;目标3：在前瞻性重新入组的研究参与者中研究长期免疫学、病毒学和耐药性结局及其相关性;目标4：通过检查研究队列亚组（n=327）的纵向库存样本，加强对病毒失败、耐药性积累以及相关人口统计学和临床因素的分析。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样本（2010年5月至2013年10月期间收集），沿着来自电子剂量监测和药物浓度的详细依从性数据;重新入组尽可能多的研究队列，进行额外的抽血;使用新型耐药性检测技术评估长期治疗失败和耐药性;使用已建立的AMPATH医疗记录系统获取每个儿童从入组AMPATH到目前的所有临床和药学数据，以检查与失败和耐药的纵向关联;并对队列的一个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纵向破坏和阻力的发展，以及哪些因素影响他们的发展的理解。这项提案是独一无二的，因为我们提出：（1）失败和耐药性的纵向调查;（2）耐药性测试的创新方法;（3）依从性，药物浓度和其他临床数据的详细调查，以影响资源有限环境中的儿科HIV护理。