Dynamics of HIV-infection, Oral Innate Immunity and The Development of Oral Diseases in Children

HIV感染动态、口腔先天免疫和儿童口腔疾病的发展

• 批准号: 10534585
• 负责人: Whasun Oh Chung
• 金额: $ 23.36万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10534585
• 关键词: AIDS/HIV problem; Adolescent; Affect; Bacteria; Biometry; Candida; Candida albicans; Caring; Child; Cities; Collaborations; Colony-forming units; Control Groups; Country; Data; Dendritic Cells; Dental Plaque; Dental caries; Dentistry; Development; Diabetes Mellitus; Disease Progression; Educational process of instructing; Endocrine System Diseases; Epithelial Cells; Exposure to; Funding; Genitourinary system; Growth; HIV; HIV Infections; HIV Seropositivity; HIV-1; Health Status; Hematological Disease; Hospital Referrals; Human; Immune system; Immunologic Factors; Infrastructure; Kenya; Knowledge; Length; Longitudinal Studies; Measures; Medical; Membrane; Mouth Diseases; Oral; Oral cavity; Oral health; Participant; Pharmaceutical Preparations; Play; Population; Positioning Attribute; Prevalence; Property; Proteins; RNA; Regimen; Research; Resources; Role; Saliva; Salivary; Salivary Glands; Schedule; United States National Institutes of Health; Universities; Virus; Washington; aged; antileukoprotease; antimicrobial; antimicrobial peptide; antimicrobial peptide LL-37; antiretroviral therapy; beta-Defensins; burden of illness; cathelicidin; cohort; experience; follow-up; fungus; macrophage; multidisciplinary; neutrophil; oral HIV; oral condition; oral innate immunity; pediatric human immunodeficiency virus; recruit; saliva secretion; success; therapy development; treatment adherence; virology; years lived with disability

PROJECT SUMMARY/ABSTRACT Oral diseases are among the most prevalent non-communicable diseases (NCDs) worldwide. Salivary antimicrobial peptides (AMPs) are proteins regulated by our immune system that disrupt the membrane integrity of bacteria. Their antimicrobial activity acts on bacteria as well as some viruses and fungi. While levels of cathelicidins (LL-37) and human beta defensins (hBD 2&3) have been associated with dental caries, secretory leukocyte protease inhibitor (SLPI) has been known for inhibiting the growth of Candida albicans. There is very limited data on AMPs in young children living with HIV. In Kenya, where about 5% of the population is HIV positive, there are an estimated 105,000 infected children and adolescents aged 0-14. The University of Washington and the University of Nairobi have >20 years of NIH funding studying pediatric HIV in Kenya. This collaboration is ideally positioned to conduct this exploratory study which is aligned with PAR-21-246 to assess the extent to which HIV infection influences the occurrence and progression of oral diseases among HIV/AIDS Kenyan children and to create research capacity in global oral health by expanding current lab infrastructure to allow local analysis of salivary AMPs in the context of HIV. This longitudinal study will be conducted in a cohort of children who receive care at the Jaramogi Oginga Odinga, the largest local teaching and referral hospital in western Kenya. Over 12 months, we will recruit and follow a cohort of 300 children (3-4y) stratified by presence of HIV: a) HIV-infected (HIV+/N=100), b) HIV exposed uninfected (HEU/N=100), and c) HIV unexposed uninfected (HUU/N=100; CONTROL GROUP). We will assess participants for ART adherence, length and regimen; dental plaque; CD4; HIV-1 RNA; and additional medications. Our aims are to: 1) Describe the impact of HIV infection on the secretion of salivary antimicrobial peptides at baseline and over a 12-month follow-up period. Coinciding with current HIV schedule for medical care, we will collect unstimulated saliva (baseline, 6, and 12-month assessments) to measure a comprehensive set of AMPs: LL-37, hBDs and SLPI. By stratifying by HIV exposure (HIV+, HEU, HUU), we will be able to measure AMP levels by group and assess factors associated with secretion. 2) Determine the associations between salivary AMPs and oral diseases in the context of HIV. At baseline, 6 and 12 months of the study, we will a): assess the degree to which AMPs are associated with presence and progression of oral diseases (plus candida colony forming units, saliva flow rate and pH), within the context of HIV exposure and related treatment, and b) identify factors impacting these associations. 3) Enhance existing HIV research capacity. We will expand current human and infrastructure resources to include oral health research. While currently the study of salivary AMPs is conducted out of Kenya, we will build upon existing lab assets allowing locals to conduct these analyses, thus starting a line of research that increases Kenyan research opportunities.

项目总结/摘要 口腔疾病是全世界最流行的非传染性疾病之一。唾液 抗微生物肽（AMP）是由我们的免疫系统调节的破坏膜完整性的蛋白质 细菌。它们的抗微生物活性作用于细菌以及一些病毒和真菌。虽然水平 cathelicidins（LL-37）和人β防御素（hBD 2&3）与龋齿、分泌性 已知白细胞蛋白酶抑制剂（SLPI）可抑制白色念珠菌的生长。有很 关于感染艾滋病毒的幼儿的抗艾滋病药物的数据有限。在肯尼亚，大约5%的人口是艾滋病毒携带者， 如果呈阳性，估计有105 000名0至14岁的儿童和青少年受感染。大学 华盛顿和内罗毕大学有超过20年的国家卫生研究院的资金研究儿童艾滋病毒在肯尼亚。这 合作是进行这项探索性研究的理想选择，该研究与PAR-21-246保持一致，以评估 HIV感染对HIV/AIDS患者口腔疾病发生和发展的影响程度 肯尼亚儿童，并通过扩大现有的实验室基础设施， 允许在HIV背景下对唾液AMP进行局部分析。这项纵向研究将在一个队列中进行 在当地最大的教学和转诊医院Jaramogi Oginga Odinga接受治疗的儿童人数 肯尼亚西部。在12个月内，我们将招募并随访300名儿童（3- 4岁）的队列， 艾滋病毒：a）艾滋病毒感染者（艾滋病毒+/N=100），B）接触艾滋病毒但未感染者（HEU/N=100），以及c）未接触艾滋病毒 未感染（HUU/N=100;对照组）。我们将评估参与者的ART依从性、持续时间和 方案;牙菌斑; CD 4; HIV-1 RNA;和其他药物。我们的目标是：1）描述影响 HIV感染对唾液抗菌肽分泌的影响 随访期。与目前的艾滋病治疗时间表一致，我们将收集未受刺激的唾液 （基线、6个月和12个月评估）以测量一组全面的AMP：LL-37、hBD和SLPI。通过 通过HIV暴露（HIV+，HEU，HUU）分层，我们将能够按组测量AMP水平并评估 与分泌有关的因素。2)确定唾液AMP与口腔疾病之间的关系 in the context背景of HIV艾滋病毒.在基线、研究的6个月和12个月，我们将a）：评估AMP 与口腔疾病的存在和进展有关（加上念珠菌菌落形成单位，唾液流 速率和pH值），以及B）确定影响这些的因素 协会. 3)加强现有的艾滋病毒研究能力。我们将扩大现有的人力和基础设施 资源，包括口腔健康研究。虽然目前唾液AMP的研究是在肯尼亚以外进行的， 我们将利用现有的实验室资源，让当地人进行这些分析，从而启动一系列研究 这增加了肯尼亚的研究机会。