Trajectories, predictors, and neurocognitive impact of HIV viral control among children living with HIV in Kenya

肯尼亚艾滋病毒感染儿童艾滋病病毒控制的轨迹、预测因素和神经认知影响

基本信息

批准号：
10159497
负责人：
Jillian Neary
金额：
$ 4.6万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-16 至 2024-03-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10159497
关键词：
3 year old Address Adherence Adult Africa South of the Sahara Aftercare Age Area Attention CD4 Lymphocyte Count Caregivers Cells Child Childhood Cohort Studies Complex Cytomegalovirus Cytomegalovirus Infections DNA Data Data Analyses Delayed Memory Development Disclosure Dose Drug resistance Early treatment Enrollment Epidemiology Equation Evaluation Face Failure Gaussian model Goals Growth HIV HIV therapy Highly Active Antiretroviral Therapy Immunity Immunologic Factors Immunosuppression Impulsivity Incidence Individual Infant Inflammation Kenya Learning Life Literature Malawi Methods Modeling Molecular Epidemiology Motor Neuraxis Neurocognition Neurocognitive Neurocognitive Deficit Neurons Opportunistic Infections Outcome Perinatal Pharmaceutical Preparations Proviruses RNA Regimen Research Research Personnel Sampling Short-Term Memory Site South Africa Statistical Methods Study models Survival Analysis Testing Time Training Uganda Viral Viral Load result Viral reservoir Viremia Virus Latency Zimbabwe aged antiretroviral therapy co-infection cognitive ability cognitive testing cohort executive function experience follow-up improved pediatric human immunodeficiency virus performance tests pre-doctoral sample collection skills student training therapy adherence treatment optimization treatment strategy virology

项目摘要

Project summary / Abstract: The primary goal of this project is to characterize the trajectories, predictors, and neurocognitive impact of viral control among children living with HIV in Kenya. There are approximately 1.7 million children ages 0-14 years living with HIV globally. For children living with HIV, early initiation of antiretroviral therapy (ART) is crucial to suppress viral load and recover immunity, resulting in improved survival, growth, neurocognition, and reduced likelihood of opportunistic infections. To control HIV replication, lifelong ART adherence is required, and children face unique challenges, including inappropriate drug dosing, poor adherence, and drug resistance, that make them less likely than adults to remain virally suppressed. Despite viral suppression, the viral reservoir persists as replication-competent provirus in infected cells that can reactivate when individuals living with HIV discontinue ART, resulting in rebound viremia. The viral reservoir remains the greatest challenge to post-treatment viral control and HIV cure; however, few studies have evaluated viral control and reservoirs in children. By leveraging samples and results from neurocognitive assessments performed within the 5R01HD094718 study (MPI: Drs. Grace John-Stewart and Dara Lehman), which involves two cohorts of children living with HIV with 10 years of post-ART follow up in Kenya, this project will contribute to the understanding of post-ART viral control among children living with HIV. Aim 1a will determine longitudinal trajectories and predictors of decline in HIV DNA among perinatally infected children. HIV DNA decline will be modeled using nonlinear mixed effects models and predictors will include age at ART initiation, ART regimen, baseline HIV RNA, baseline CD4, and early cytomegalovirus coinfection. Aim 1b will determine predictors of high viral reservoir among perinatally infected children on ART using generalized estimating equations. Predictors will include age at ART initiation, ART regimen, baseline HIV RNA, baseline CD4, and early cytomegalovirus coinfection. Aim 2 will determine incidence and predictors of virologic failure (HIV RNA exceeding ≥1,000, ≥400, and ≥50 copies/ml) among children who are virally suppressed at two years post-ART initiation using Cox regression. Predictors will include age at ART initiation, baseline CD4, ART regimen, caregiver disclosure, and child adherence to ART. Lastly, this project will determine the impact of viral control on neurocognition among children living with HIV. Aim 3 will determine the association between CD4, HIV RNA, HIV DNA, and reservoir levels and neurocognitive outcomes using generalized estimating equations. Findings from this project will optimize early treatment and potentially contribute to HIV cure strategies. This research plan will provide the F31 candidate with rigorous predoctoral training, including 1) advanced epidemiologic statistical methods including analyses of complex longitudinal data, 2) experience with molecular epidemiology related to pediatric HIV, and 3) content-area expertise in neurocognition among children living with HIV.

项目摘要 /摘要：该项目的主要目标是表征病毒的轨迹，预测因子和神经认知影响在肯尼亚艾滋病毒的儿童中控制。大约有170万儿童0-14岁全球与艾滋病毒一起生活。对于患有艾滋病毒的儿童，抗逆转录病毒疗法（ART）的早期开始对抑制病毒负荷和恢复免疫力，从而提高生存率，生长，神经认知并降低机会性感染的可能性。为了控制艾滋病毒的复制，需要终生的艺术依从性，孩子们面临独特的挑战，包括不适当的药物给药，依从性差和耐药性，使与成年人相比，他们不太可能被病毒抑制。尽管病毒抑制，病毒储层仍然存在作为感染细胞中的复制能力病毒，当停止HIV的个体时，可以重新激活艺术，导致反弹病毒血症。病毒储层仍然是治疗后病毒的最大挑战控制和艾滋病毒治愈；但是，很少有研究评估儿童的病毒控制和储藏。通过利用在5R01HD094718研究中进行的样本和神经认知评估的结果（MPI：DRS。格蕾丝·约翰·斯图尔特（Grace John-Stewart）和达拉·雷曼肯尼亚的艺术后跟进，该项目将有助于理解对艺术后的病毒控制患有艾滋病毒的孩子。 AIM 1A将确定HIV DNA下降的纵向轨迹和预测指标在围产期感染的儿童中。 HIV DNA下降将使用非线性混合效应模型和预测因素将包括Art Initiative的年龄，ART方案，基线HIV RNA，基线CD4和早期巨细胞病毒共感染。 AIM 1B将确定围产期感染中高病毒储层的预测因子使用广义估计方程式的艺术儿童。预测因素将包括艺术倡议的年龄方案，基线HIV RNA，基线CD4和早期巨细胞病毒共感染。 AIM 2将确定病毒学衰竭的发生率和预测因子（HIV RNA超过≥1,000，≥400和≥50份/ml）使用Cox回归的两年后两年后，几乎被抑制的儿童。预测因素将包括 Art Initiative年龄，基线CD4，艺术方案，看护人披露以及对艺术的遵守。最后，这个项目将确定病毒控制对艾滋病毒儿童神经认知的影响。目标3意志确定CD4，HIV RNA，HIV DNA和储层水平与神经认知结果之间的关联使用广义估计方程。该项目的发现将优化早期治疗，并可能有助于艾滋病毒治愈策略。该研究计划将为F31候选人提供严格的候选人培训，包括1）高级流行病学统计方法，包括对复杂纵向数据的分析 2）具有与儿科HIV相关的分子流行病学经验，以及3）内容区域专业知识艾滋病毒感染儿童的神经认知。