Pediatric HIV/AIDS Cohort Study (PHACS) 2020

儿科艾滋病毒/艾滋病队列研究 (PHACS) 2020

• 批准号: 10290224
• 负责人: Ellen Gould Chadwick
• 金额: $ 32.23万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10290224
• 关键词: 16S ribosomal RNA sequencing; Address; Adolescent; Adult; Age; Anti-Retroviral Agents; Antibody titer measurement; Area; Automobile Driving; Award; Biological Assay; Biological Markers; Body Composition; Cardiac; Cervical Cancer Screening; Child; Child Health; Clinical; Consent; Cytology; Data; Development; Diagnosis; Disease; Disease remission; Epigenetic Process; Epithelial; Event; Exposure to; General Population; Genetic; Grant; Guidelines; HIV; HIV Infections; Hearing; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Immunologic Factors; Infant; Infant Health; Infection; Inflammation; Inflammatory; Infrastructure; Kidney; Lactobacillus; Lead; Link; Literature; Lung; Malignant Squamous Cell Neoplasm; Malignant neoplasm of cervix uteri; Measures; Metabolic; Monitor; Morbidity - disease rate; Natural History; Neurologic; Nitrosamines; Nutritional; Oncogenic; Oral health; Organ; Pathway interactions; Pediatric HIV/AIDS Cohort Study; Perinatal; Perinatal transmission; Persons; Pharmaceutical Preparations; Policies; Pregnant Women; Prevention; Probiotics; Prospective cohort study; Protocols documentation; Pulmonary Heart Disease; Research; Research Project Grants; Resources; Risk Factors; Role; Safety; Sampling; Self Administration; Series; Testing; Toxic effect; Translating; Vaccinated; Vaccines; Vagina; Woman; Youth; biobank; bone; carcinogenicity; cardiovascular disorder risk; chemokine; chronic infection; clinical biomarkers; cytokine; design; dysbiosis; high risk; in utero; innovation; metabolic profile; metabolomics; microbial; microbiome; multidisciplinary; multiplex assay; neuroimaging; perinatal HIV; perinatal women; postnatal; predictive marker; prevent; programs; reproductive outcome; screening guidelines; transmission process; treatment response; treatment strategy; vaccination strategy; vaginal microbiome; virology; young adult; young woman

Project Summary/Abstract Each year, there are more than 1 million pregnant women living with HIV (PWLHIV) who receive antiretroviral medications (ARVs) for treatment and perinatal and postnatal HIV transmission prevention, with new ARVs introduced at a rapid pace. Although maternal use of ARVs has successfully reduced perinatal HIV transmission, there remains a clear need to monitor the safety of in utero ARV for infant and child health. PHACS 2020 is designed as a Program Project P01 grant, consisting of four support Cores and 2-4 research projects. This multidisciplinary, interdisciplinary, transdisciplinary and synergistic P01 will address the most critical scientific questions for children, youth and young adults exposed to or living with HIV. This supplement specifically addresses the research agenda proposed in the prime award: PHACS2020 Adolescent Master Protocol Up Series (AmpUP). Over 300,000 women die each year from squamous cell cancers of the cervix caused by persistent infection with high-risk (i.e. oncogenic) human papillomavirus (hrHPV). The HPV vaccine has been a transforming event, capable of preventing cervical cancer globally. Although HIV infection is an established risk factor for HPV-associated cancers in adults, the natural history of HPV among young women living with perinatal HIV (YWLPHIV) is not well established. In a recent PHACS study of HPV-vaccinated youth, YWLPHIV had lower HPV antibody titers than perinatally HIV exposed but uninfected young women (YWLPHEU) and high rates of abnormal cytology. It is essential to understand factors associated with persistence of hrHPV vaccine and non-vaccine HPV types in HPV vaccinated YWLHIV. Vaginal microbiome dysbiosis has been associated with hrHPV persistence, possibly through dysbiosis-induced inflammation and consequent epithelial disruption with release of known carcinogenic products. In this study, we propose to take advantage of PHACS unique infrastructure and biorepository. From assays on annual vaginal samples collected by women in PHACS III, we will identify women with hrHPV persistence vs clearance and determine the role of microbial dysbiosis (16S rRNA sequencing) and inflammation (multiplex cytokine assays metabolic profiles) on hrHPV persistence in YWLPHIV and YWLPHEU who have been vaccinated against HPV. The results of this study will be critical for developing treatment strategies (such as the use of vaginal probiotics) and cervical cancer screening guidelines for WLPHIV in resourced and resource limited settings.

项目概要/摘要 每年，有超过 100 万感染艾滋病毒 (PWLHIV) 的孕妇接受抗逆转录病毒治疗 用于治疗和预防围产期和产后艾滋病毒传播的药物（抗逆转录病毒药物），包括新的抗逆转录病毒药物 快速推出。尽管孕产妇使用抗逆转录病毒药物已成功减少围产期艾滋病毒 传播，显然仍然需要监测宫内抗逆转录病毒药物对婴儿和儿童健康的安全性。 PHACS 2020 被设计为计划项目 P01 赠款，由四个支持核心和 2-4 个研究组成 项目。这个多学科、跨学科、跨学科和协同的 P01 将解决最 接触艾滋病毒或感染艾滋病毒的儿童、青年和年轻人面临的关键科学问题。 本补充材料专门讨论了大奖中提出的研究议程： PHACS2020 青少年主协议升级系列 (AmpUP)。每年有超过 300,000 名女性死于 由高危（即致癌）人类持续感染引起的子宫颈鳞状细胞癌 乳头状瘤病毒（hrHPV）。 HPV 疫苗是一项变革性事件，能够预防宫颈癌 全球癌症。尽管 HIV 感染是成人 HPV 相关癌症的既定危险因素， 感染围产期 HIV 的年轻女性 (YWLPHIV) 的 HPV 自然史尚未明确。在一个 最近针对接种 HPV 疫苗的青少年进行的 PHACS 研究显示，YWLPHIV 的 HPV 抗体滴度低于围产期 HIV 抗体滴度 暴露但未感染的年轻女性（YWLPHEU）和细胞学异常率很高。至关重要的是 了解 HPV 中与 hrHPV 疫苗和非疫苗 HPV 类型持续存在相关的因素 接种了 YWLHIV 疫苗。阴道微生物群失调可能与 hrHPV 持续存在相关 通过菌群失调引起的炎症和随后的上皮破坏并释放已知的 致癌产品。在这项研究中，我们建议利用 PHACS 独特的基础设施和 生物储存库。通过对 PHACS III 中女性每年采集的阴道样本进行分析，我们将确定 具有 hrHPV 持续性与清除率的女性，并确定微生物失调的作用（16S rRNA 测序）和炎症（多重细胞因子测定代谢谱）对 hrHPV 持久性的影响 已接种 HPV 疫苗的 YWLPHIV 和 YWLPHEU。这项研究的结果对于 制定治疗策略（例如使用阴道益生菌）和宫颈癌筛查 资源丰富和资源有限环境中的 WLPHIV 指南。