Pediatric HIV and Cancer Epidemiology

儿童艾滋病毒和癌症流行病学

• 批准号: 10223901
• 负责人: Michael E Scheurer
• 金额: $ 17.22万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-25 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10223901
• 关键词: 14 year old; AIDS related cancer; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Acute; Address; Adult; Africa; Africa South of the Sahara; Biological Markers; Blood; Cancer Burden; Caring; Cells; Child; Childhood; Clinic; Clinical; Clinical Data; Collection; Computerized Medical Record; Data; Diagnosis; Disease; Environment; Epidemiology; Future; Goals; HIV; HIV Infections; Human Herpesvirus 4; Human Herpesvirus 8; Immune; Immune system; Incidence; Infection; International; Invaded; Kaposi Sarcoma; Laboratories; Life; Literature; Lymphoma; Malignant Childhood Neoplasm; Malignant Neoplasms; Malnutrition; Medicine; Pediatric Hospitals; Pediatric epidemiology; Plasma; Population; Prevalence; Protocols documentation; Recording of previous events; Research; Resources; Risk; Risk Factors; Screening for cancer; Severities; Site; System; Texas; Time; Update; Ursidae Family; Viral Load result; Viral Markers; Virus; antiretroviral therapy; base; cancer biomarkers; cancer diagnosis; cancer epidemiology; cancer risk; chemokine; clinical risk; cohort; college; comorbidity; cytokine; epidemiology study; experience; high risk; high risk population; infection related cancer; novel; pediatric human immunodeficiency virus; risk prediction

Project 1: Epidemiology of and Risk Prediction for Childhood Cancers in the Context of HIV/AIDS in Africa Sub-Saharan Africa (SSA) disproportionately bears the burden of pediatric HIV/AIDS, having approximately 90% of the 1.7 million pediatric cases of HIV. While substantial progress has been made in recent years to limit the number of new cases of HIV among children, there are still an estimated 1.6 million children living with HIV in SSA. These HIV-infected children are at a higher risk for developing cancer as a result of their disease. The epidemiology of HIV-related malignancies among adults has been fairly extensively studied; however, few epidemiologic studies on cancer among children with HIV have been conducted. Our long-term goal is to determine which HIV-infected children are at highest risk of developing a malignancy. To address these gaps in the epidemiology of pediatric HIV-related malignancies in SSA, we propose the following aims: 1. Calculate the prevalence and incidence of cancers among HIV+ children by expanding and updating a cohort of HIV+ children who are treated and followed at the BIPAI Centers of Excellence. We will leverage both the high-quality electronic medical record system in the BIPAI CoE and affiliated clinic network and the large population of HIV-infected children who have been treated at the CoEs since 2004 to understand the distribution of cancers in this high-risk population. Hypotheses: 1) The incidence of certain infection-related cancers will be higher among HIV-infected children age 14 years or younger, and 2) there will be a lower incidence of HIV-associated cancers (e.g., KS) over the timeframe of this cohort compared to historical data, while the incidence of other non-AIDS defining cancers will be higher. 2. Determine the impact of clinical risk factors on pediatric HIV-related malignancy risk in SSA. We will assess the impact of risk factors such as timing of anti-retroviral treatment, HIV stage at cancer diagnosis, severe acute malnutrition at cancer diagnosis, and geoclimatic differences on HIV-related malignancy risk of children living in SSA. We will also assess whether risk of developing HIV-related malignancies is influenced by history of infections and other co-morbidities. Hypothesis: Factors related to a child's HIV infection severity and early life environment underlie risk of developing pediatric HIV-related malignancies in SSA. 3. Identify plasma biomarkers that are more abundant among HIV+ children diagnosed with cancer. Based on evidence from the literature and our own preliminary data, we will compare a standard set of cytokines/chemokines, and markers of virus burden, in 4 groups of children: 1) HIV+/Cancer+, 2) HIV+/Cancer-, 3) HIV-/Cancer+, and 4) HIV-/Cancer-. The goal is to identify biomarkers of cancer risk in HIV+ children that could be utilized with the clinical factors identified in Aim 2 to develop a novel paradigm for cancer screening in this high-risk population. Hypothesis: There are both specific cancer- and HIV-related differences detectable in the plasma of children who develop HIV-related malignancies compared to those who do not.

项目1：艾滋病毒/艾滋病背景下的儿童癌症流行病学和风险预测 非洲 撒哈拉以南非洲（SSA）承担着不成比例的儿科艾滋病毒/艾滋病负担， 170万儿童艾滋病病例中的90%。虽然近年来取得了重大进展， 尽管限制了儿童中艾滋病毒新病例的数量，但估计仍有160万儿童感染艾滋病毒， 艾滋病在SSA这些感染艾滋病毒的儿童由于其疾病而患癌症的风险更高。 成人中HIV相关恶性肿瘤的流行病学已得到相当广泛的研究;然而， 对感染艾滋病毒的儿童进行了癌症流行病学研究。我们的长期目标是 确定哪些感染艾滋病毒的儿童患恶性肿瘤的风险最高。弥补这些差距 在SSA儿童HIV相关恶性肿瘤的流行病学中，我们提出以下目标： 1.计算艾滋病毒阳性儿童中癌症的流行率和发病率， 一群在BIPAI卓越中心接受治疗和随访的艾滋病毒阳性儿童。 我们将利用BIPAI卓越中心和附属诊所的高质量电子病历系统 自2004年以来，有大量艾滋病毒感染儿童在欧洲委员会接受治疗， 了解癌症在这一高危人群中的分布情况。假设：1）某些疾病的发病率 感染相关癌症在14岁或14岁以下的艾滋病毒感染儿童中会更高，2） 艾滋病毒相关癌症的发病率较低（例如，KS）在该队列的时间范围内， 根据历史数据，而其他非艾滋病定义的癌症的发病率将更高。 2.确定临床危险因素对SSA儿童HIV相关恶性肿瘤风险的影响。 我们将评估风险因素的影响，如抗逆转录病毒治疗的时间，艾滋病毒在癌症阶段 诊断，癌症诊断时严重急性营养不良，以及艾滋病毒相关的地理气候差异 生活在SSA的儿童的恶性肿瘤风险。我们还将评估是否有风险发展艾滋病毒相关的 恶性肿瘤受感染史和其他合并症的影响。假设：与a相关的因素 儿童的艾滋病毒感染严重程度和早期生活环境是儿童艾滋病毒相关疾病风险的基础。 SSA中的恶性肿瘤。 3.确定在被诊断患有癌症的HIV+儿童中更丰富的血浆生物标志物。 根据文献中的证据和我们自己的初步数据，我们将比较一组标准的 细胞因子/趋化因子和病毒负荷标志物，在4组儿童中：1）HIV+/癌症+，2）HIV+/癌症-， 3)HIV-/癌症+，和4）HIV-/癌症-。目标是确定HIV阳性儿童癌症风险的生物标志物， 可以与目标2中确定的临床因素一起使用，以开发一种新的癌症筛查模式， 这个高危人群。假设：可以检测到与癌症和艾滋病毒相关的特定差异 与未患艾滋病相关恶性肿瘤的儿童相比，