Pediatric HIV/AIDS Cohort Study (PHACS) 2020

项目总结/摘要 每年有100多万感染艾滋病毒的孕妇接受抗逆转录病毒治疗 用于治疗和预防围产期及产后艾滋病毒传播的抗逆转录病毒药物，以及新的抗逆转录病毒药物 以快速的速度推出。虽然母亲使用抗逆转录病毒药物成功地减少了围产期艾滋病毒感染， 尽管抗逆转录病毒药物在子宫内传播的风险很小，但仍明显需要监测子宫内抗逆转录病毒药物对婴幼儿健康的安全性。 PHACS 2020被设计为计划项目P01赠款，包括四个支持核心和2-4个研究 项目这一多学科、跨学科、跨学科和协同的P01将解决大多数 关键的科学问题，儿童，青年和年轻的成年人接触或感染艾滋病毒。 本附录专门针对主要奖项中提出的研究议程： PHACS 2020青少年主协议升级系列（AmpUP）。每年有30多万妇女死于 由高危（即致癌）人类病毒持续感染引起的宫颈鳞状细胞癌 乳头瘤病毒（hrHPV）。HPV疫苗是一个转变事件，能够预防宫颈癌。 全球癌症虽然HIV感染是成人HPV相关癌症的既定危险因素， 感染围产期艾滋病毒的年轻妇女的HPV自然史（YWLPHIV）尚未得到很好的确定。中 最近一项针对接种HPV疫苗的年轻人的PHACS研究表明，YWLPHIV的HPV抗体滴度低于围产期HIV 暴露但未受感染的年轻妇女（YWLPHEU）和细胞学异常率高。有必要 了解HPV中hrHPV疫苗和非疫苗HPV类型持续存在的相关因素 接种YWLHIV。阴道微生物组生态失调与hrHPV持续存在相关，可能与 通过生态失调诱导的炎症和随后的上皮破坏， 致癌产品。在这项研究中，我们建议利用PHACS独特的基础设施， 生物储藏室从PHACS III中女性每年收集的阴道样本的分析中，我们将确定 hrHPV持续存在与清除的妇女，并确定微生物生态失调（16 S rRNA）的作用 测序）和炎症（多重细胞因子测定代谢谱）对hrHPV持续性的影响。 接种过HPV疫苗的YWLPHIV和YWLPHEU。这项研究的结果将是至关重要的， 制定治疗策略（如使用阴道益生菌）和宫颈癌筛查 在资源和资源有限的情况下制定WLPHIV指南。

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.