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.

项目概要/摘要 口腔疾病是全球最流行的非传染性疾病（NCD）之一。唾液 抗菌肽 (AMP) 是由我们的免疫系统调节的蛋白质，可破坏细胞膜的完整性 的细菌。它们的抗菌活性作用于细菌以及一些病毒和真菌。虽然水平 导管素 (LL-37) 和人类 β 防御素 (hBD 2&3) 与龋齿、分泌 白细胞蛋白酶抑制剂（SLPI）因抑制白色念珠菌的生长而闻名。有非常 有关感染艾滋病毒幼儿的 AMP 的数据有限。在肯尼亚，大约 5% 的人口感染了艾滋病毒 据估计，有 105,000 名 0-14 岁儿童和青少年被感染。大学 华盛顿大学和内罗毕大学 20 年来一直资助 NIH 资助肯尼亚儿童艾滋病毒研究。这 合作非常适合开展这项探索性研究，该研究与 PAR-21-246 一致，以评估 HIV感染对HIV/AIDS口腔疾病发生和进展的影响程度 肯尼亚儿童并通过扩大现有的实验室基础设施来建立全球口腔健康的研究能力 允许在 HIV 背景下对唾液 AMP 进行本地分析。这项纵向研究将在队列中进行 的儿童在 Jaramogi Oginga Odinga 接受护理，这是当地最大的教学和转诊医院 肯尼亚西部。在 12 个月的时间里，我们将招募并跟踪 300 名儿童（3-4 岁），并按其在场情况进行分层 HIV 感染者：a) HIV 感染者 (HIV+/N=100)，b) HIV 暴露者未感染者 (HEU/N=100)，c) HIV 暴露者未感染者 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 养生法；牙菌斑； CD4； HIV-1 RNA；和其他药物。我们的目标是： 1) 描述影响 HIV 感染对基线和 12 个月内唾液抗菌肽分泌的影响 随访期。与当前艾滋病毒医疗护理时间表相一致，我们将收集未受刺激的唾液 （基线、6 个月和 12 个月评估）来衡量一套全面的 AMP：LL-37、hBD 和 SLPI。经过 根据 HIV 暴露情况（HIV+、HEU、HUU）进行分层，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联 在艾滋病毒的背景下。在基线、研究的第 6 个月和第 12 个月，我们将 a)：评估 AMP 的程度 与口腔疾病的存在和进展有关（加上念珠菌菌落形成单位、唾液流量 b) 确定影响这些因素的因素 协会。 3) 增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 的研究是在肯尼亚进行的， 我们将利用现有的实验室资产，允许当地人进行这些分析，从而开始一系列研究 这增加了肯尼亚的研究机会。