Pediatric HIV/AIDS Cohort Study (PHACS) 2020

项目摘要/摘要 每年有100多万名携带艾滋病毒(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(ARV)，以及新的ARV 以快速的步伐引入。尽管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 尽管存在传播风险，但显然仍有必要监测宫内抗逆转录病毒的安全性，以保障婴儿和儿童的健康。 PHACS 2020被设计为项目P01赠款，由四个支持核心和2-4项研究组成 项目。这份多学科、跨学科、跨学科和协同的P01将解决大多数 对接触艾滋病毒或感染艾滋病毒的儿童、青年和青壮年提出关键科学问题。 本附录专门针对PRIME奖中提出的研究议程： PHACS2020青少年主协议UP系列(AmpUP)。每年有30多万妇女死于 高危(致癌)人群持续感染引起的宫颈鳞状细胞癌 人乳头瘤病毒(HrHPV)。HPV疫苗是一个变革性的事件，能够预防宫颈 全球范围内的癌症。虽然艾滋病毒感染是成人HPV相关癌症的既定危险因素，但 感染围产期艾滋病毒(YWLPHIV)的年轻女性中HPV的自然病史尚未得到很好的证实。在一个 最近PHACS对接种HPV疫苗的年轻人的研究，YWLPHIV的HPV抗体效价低于围产期HIV 暴露但未受感染的年轻女性(青年会)和细胞学异常率高。这是至关重要的 了解人乳头瘤病毒疫苗和非疫苗型人乳头瘤病毒在人乳头瘤病毒中持续存在的相关因素 接种YWLHIV疫苗。阴道微生物群失调可能与hrHPV持续存在有关 通过生态失调引起的炎症和随之而来的上皮破坏，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。从PHACS III上女性每年收集的阴道样本的化验中，我们将确定 女性hrHPV持续与清除和确定微生物失调(16S RRNA)的作用 测序)和炎症(多重细胞因子分析代谢谱)对hrHPV持久性的影响 已经接种了HPV疫苗的YWLPHIV和YWLPHEU。这项研究的结果将对 制定治疗策略(如使用阴道益生菌)和宫颈癌筛查 WLPHIV在资源有限和资源有限的情况下的指南。

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.