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.

 说明(申请人提供)：抗逆转录病毒疗法(ART)的耐药性对艾滋病毒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，关于儿童中病毒失败率和耐药性发展的纵向数据很少，特别是在撒哈拉以南非洲，那里90%以上的艾滋病毒感染儿童生活在那里。我们研究团队的长期目标是为在资源有限的情况下改善艾滋病毒感染儿童和青少年的临床疾病管理提供新的证据。这项建议的目的是纵向调查肯尼亚西部685名艾滋病毒感染儿童中先前建立的仔细描述的队列中的治疗失败、耐药性和相关因素。这项工作将在美国-肯尼亚长期合作伙伴关系-学术模式提供获得医疗保健(AMPATH)-范围内进行，该模式目前在肯尼亚65个临床站点为70,000多名成人和儿童艾滋病毒感染者提供护理。我们将利用AMPATH优秀的基础设施，以及之前由NIH资助的建立这一儿童队列的研究(Vreeman：1K23MH087225)，提供关于五年内失败和抵抗发展的新的和重要的数据。该提案的具体目标是：目标1：确定病毒失败的流行率，并在685名接受一线抗逆转录病毒治疗的肯尼亚围产期感染艾滋病毒的儿童的回顾研究队列中检查耐药突变模式。目标2：调查特定的依附模式、抗逆转录病毒药物水平和其他人口统计学和临床因素与病毒失效和耐药性之间的关系；目标3：研究预期重新纳入的研究参与者的长期免疫学、病毒学和耐药性结果及其相关性；目标4：通过检查可用于研究队列子集的纵向样本，加强对病毒失效、耐药性积累和相关人口统计学和临床因素的分析(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银行血液样本(在2010年5月至2013年10月期间收集)，以及电子剂量监测和药物浓度的详细依从性数据；重新招募尽可能多的研究队列进行额外的抽血；利用新的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医疗记录系统获得从AMPATH登记到现在的每个儿童的所有临床和药学数据，以检查失败和耐药性的纵向关联；并对队列子组的当前依从性进行预期的电子剂量监测。这项研究将对理解纵向破坏和抗力发展以及哪些因素影响它们的发展产生重大影响。这一建议是独特的，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；以及(3)详细调查依从性、药物浓度和其他临床数据，以影响资源有限的情况下的儿科艾滋病毒护理。