Research Project 2 Molecular, viral and genetic epidemiology of virally induced AIDS-defining cancers affecting Argentina population with highest risk for HIV infection

研究项目 2 影响艾滋病毒感染风险最高的阿根廷人口的病毒引起的艾滋病定义癌症的分子、病毒和遗传流行病学

• 批准号: 10246319
• 负责人: Pedro Enrique Cahn
• 金额: $ 3.13万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246319
• 关键词: AIDS related cancer; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Acyclovir; Address; Affect; Animal Model; Anti-Retroviral Agents; Anus; Area; Argentina; Argentine; Award; Basic Science; Biological; Blood specimen; CD4 Lymphocyte Count; Cancer Burden; Caring; Cell Line; Cells; Characteristics; Chlamydia; Clinical; Clinical Data; Cohort Studies; Collaborations; Collection; Communities; Coupled; Cytology; DNA Virus Infections; Development; Diagnosis; Disease; Drug usage; Enrollment; Epidemiology; Funding; Gene Expression; General Population; Genes; Genetic Determinism; Genetic study; Genomics; Goals; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Health; Health Services Accessibility; Health system; High Prevalence; Hormones; Hospitals; Human; Human Herpesvirus 8; Human Papillomavirus; Human papilloma virus infection; In Vitro; Incidence; Income; Individual; Infection; International; Intervention; Kaposi Sarcoma; Knowledge; Lesion; Life Expectancy; Location; Longitudinal Studies; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of anus; Modeling; Molecular; Molecular Abnormality; Molecular Epidemiology; Molecular Genetics; Monitor; Mutation; North America; Oncogenic; Oral; Pathologic; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Policies; Population; Portraits; Positioning Attribute; Prevalence; Prospective cohort; Registries; Research; Research Personnel; Research Priority; Research Project Grants; Research Support; Research Training; Risk Factors; Sampling; Serology; Site; South America; Specimen; Subgroup; Syphilis; Testing; Time; Tissue Sample; Treatment outcome; Tumor Tissue; United States National Institutes of Health; Variant; Viral; Viral Epidemiology; Viral Load result; Viral hepatitis; Viremia; Virus; Virus Diseases; Work; advocacy organizations; base; cancer risk; career; co-infection; cohort; comorbidity; driver mutation; exome sequencing; genetic epidemiology; health disparity; high risk; high risk population; improved; in vivo; low and middle-income countries; men; neoplastic; premalignant; prospective; repository; research clinical testing; sex; social structure; transcriptome; transcriptome sequencing; transcriptomics; transgender; transgender women; transsexual; transvestite; treatment disparity; treatment response; tumor; working group

RESEARCH PROJECT 2 SUMMARY JULY 2017-JUNE 2023 Men having sex with men (MSM) and transgender women (TGW) are the most affected populations by HIV, present high prevalence of KSHV and HPV, and two malignant conditions associated to these virus (Kaposi Sarcoma and Anal Squamous Cell Carcinoma, respectively) are also disproportionally affecting these groups. KS continues being the most important AIDS associated cancer in LMICs. On the other hand, ART changed the course of HIV and increased life expectancy, but HPV persistence represents a continued risk factor for anal cancer. The aims of this project are 1) to increase the knowledge about prevalence, incidence, and clearance of KSHV and HR-HPV among high risk individuals (MSM and TG individuals with and without HIV) and factors associated to clinical progression 2) to create a repository of prospective and retrospective samples of KS and ASCC cou- pled to clinical data and 3) to explore in KS and ASCC the molecular portrait and viral factors by Whole-Exome sequencing in parallel with RNA-Seq profiling comparing the mutational and gene expression profiles of samples for identify specific transcriptome. We will accomplish these aims studying two populations: a) a cohort of individuals at high risk of developing KS and ASCC 220 MSM and 110 transgender women, HIV positive and HIV negative) in whom we will assess every 6 months during 4 years the prevalence, incidence, and associated factors for KSHV infection and HPV infection. c) a repository of clinical information and biological samples of individual with KS and ASCC. This registry will involve two components, the prospective component that will collect clinical data and samples from patients in study for KS or ASCC (15-30/year) and a retrospective component aimed to provide limited clinical information and remnants of pathological specimens at 6 sites (400 KS and 200 ASCC). All the material will be available also for Basic and Translational Projects 1 and 2. With these aims our research contributes to several areas defined by NIH as high priority research on HIV/AIDS, including the focus in malignances, basic research on genetic determinants of co-morbidities and research to reduce health disparities in the treatment outcomes of people living with HIV. Further, this research will support research capacity development in a low- and middle-income settings. Accordingly, we aim to address several urgent health questions, which will inform the development of a range of policies and interventions throughout South and North America. The long-term objective of this study is to catalyze international collaboration among US and Argentinean investigators to improve capacity to reduce the cancer burden among HIV individuals.

研究项目 2 概要 2017年7月-2023年6月 男男性行为者 (MSM) 和变性女性 (TGW) 是受艾滋病毒影响最严重的人群， 目前 KSHV 和 HPV 的流行率很高，以及与这些病毒相关的两种恶性疾病（卡波西病毒） 分别为肉瘤和肛门鳞状细胞癌） 也对这些群体产生了不成比例的影响。 KS 仍然是中低收入国家中最重要的艾滋病相关癌症。另一方面，ART改变了 HIV 的病程和预期寿命的延长，但 HPV 的持续存在是肛门感染的持续危险因素 癌症。 该项目的目的是 1) 增加对 KSHV 的患病率、发病率和清除率的了解 高危人群（感染和未感染 HIV 的 MSM 和 TG 个体）中的 HR-HPV 和 HR-HPV 以及相关因素 2) 创建 KS 和 ASCC 的前瞻性和回顾性样本库 提供临床数据，3) 通过全外显子组探索 KS 和 ASCC 的分子肖像和病毒因子 测序与 RNA-Seq 分析并行比较样品的突变和基因表达谱 用于识别特定的转录组。 我们将通过研究两个人群来实现这些目标：a) 一群患有 KS 高风险的个体 以及 ASCC 220 名男男性行为者和 110 名跨性别女性（HIV 阳性和 HIV 阴性），我们将对他们进行评估 4 年中 6 个月 KSHV 感染和 HPV 感染的患病率、发病率和相关因素。 c) KS 和 ASCC 患者的临床信息和生物样本存储库。该注册表将 涉及两个部分，前瞻性部分将收集患者的临床数据和样本 针对 KS 或 ASCC 的研究（15-30/年）和旨在提供有限临床信息的回顾性部分 以及 6 个地点（400 KS 和 200 ASCC）的病理标本残留物。所有材料都将可用 也适用于基础项目 1 和转化项目 2。 出于这些目标，我们的研究为 NIH 定义的艾滋病毒/艾滋病高度优先研究的几个领域做出了贡献， 包括重点关注恶性肿瘤、共病遗传决定因素的基础研究以及相关研究 减少艾滋病毒感染者治疗结果的健康差异。此外，这项研究将支持 低收入和中等收入环境中的研究能力发展。因此，我们的目标是解决几个问题 紧迫的健康问题将为制定一系列政策和干预措施提供信息 南美洲和北美洲。本研究的长期目标是促进国际合作 美国和阿根廷研究人员致力于提高减少艾滋病毒感染者癌症负担的能力。