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.

项目总结/文摘