The impact of early antiretroviral treatment initiation on measles immunity among children living with HIV

早期开始抗逆转录病毒治疗对艾滋病毒感染儿童麻疹免疫力的影响

• 批准号: 10308551
• 负责人: Catherine Gayle Sutcliffe
• 金额: $ 16.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10308551
• 关键词: 5 year old; 9 year old; Address; Adoption; Africa South of the Sahara; African; Aftercare; Age; Age-Months; Antibodies; Caring; Case Study; Child; Clinic; Cohort Studies; Collaborations; Communicable Diseases; Communities; Control Groups; Democratic Republic of the Congo; Diagnosis; Disease; Disease Outbreaks; Disease Progression; Early Diagnosis; Early treatment; Enrollment; Ensure; Epidemiology; Fostering; Funding; HIV; Heterogeneity; Immune response; Immunity; Immunization; Immunoglobulin G; Infant; Institution; International; Knowledge; Madagascar; Malaria; Measles; Measles virus; Mosses; National Institute of Allergy and Infectious Disease; Nigeria; Parents; Participant; Pattern; Perinatal; Prior Therapy; Public Health Schools; Recommendation; Reporting; Research; Research Personnel; Research Priority; Resources; Rural; Sampling; Site; Testing; Time; Trust; United States National Institutes of Health; Vaccination; Vaccines; World Health Organization; Zambia; age group; antiretroviral therapy; base; cohort; design; immune function; immune reconstitution; infancy; insight; pediatric human immunodeficiency virus; response; seropositive; work-study; 5 year old; 9 year old; Address; Adoption; Africa South of the Sahara; African; Aftercare; Age; Age-Months; Antibodies; Caring; Case Study; Child; Clinic; Cohort Studies; Collaborations; Communicable Diseases; Communities; Control Groups; Democratic Republic of the Congo; Diagnosis; Disease; Disease Outbreaks; Disease Progression; Early Diagnosis; Early treatment; Enrollment; Ensure; Epidemiology; Fostering; Funding; HIV; Heterogeneity; Immune response; Immunity; Immunization; Immunoglobulin G; Infant; Institution; International; Knowledge; Madagascar; Malaria; Measles; Measles virus; Mosses; National Institute of Allergy and Infectious Disease; Nigeria; Parents; Participant; Pattern; Perinatal; Prior Therapy; Public Health Schools; Recommendation; Reporting; Research; Research Personnel; Research Priority; Resources; Rural; Sampling; Site; Testing; Time; Trust; United States National Institutes of Health; Vaccination; Vaccines; World Health Organization; Zambia; age group; antiretroviral therapy; base; cohort; design; immune function; immune reconstitution; infancy; insight; pediatric human immunodeficiency virus; response; seropositive; work-study

PROJECT SUMMARY/ABSTRACT There are an estimated 1.7 million children living with HIV globally, with approximately 90% in sub-Saharan Africa. Despite antiretroviral treatment, many of these children remain susceptible to vaccine-preventable diseases, including measles. Consequently, the World Health Organization’s Strategic Advisory Group of Experts (SAGE) on immunization recommended in 2015 that children living with HIV and receiving treatment be revaccinated against measles. With earlier diagnosis in infancy in recent years, children living with HIV may now be initiating treatment prior to measles vaccination at 9 months of age. The impact of this change in the relative timing of measles vaccination and treatment on short and long-term immunity to measles is not fully known. SAGE found that there was insufficient evidence to make recommendations for children who start treatment before measles vaccination and identified this as a research priority. This proposal will bring together a team of institutions and investigators to address this gap and evaluate the short and long-term impact of early treatment initiation on antibodies to measles among children living with HIV in Zambia. The proposed research aligns with the priorities of the National Institute of Allergy and Infectious Diseases to better understand immune responses to infectious diseases and to foster international scientific collaborations. The studies will be conducted at an established research site in rural southern Zambia and will be nested within two ongoing studies: 1) a long-standing cohort study of children living with HIV and receiving care at an HIV clinic; and 2) a community-based study of malaria. The proposed studies will test stored samples collected from these studies for measles antibodies to address the research questions. For Aim 1, samples collected 6-12 months after treatment initiation will be tested from children younger than 5 years of age and enrolled in the pediatric HIV cohort. The level of measles antibodies will be compared across participants initiating treatment at different ages (<9 months of age and prior to measles vaccination, 9 months to 1.9 years of age, and 2.0 to 4.9 years of age). For Aim 2, samples collected from children enrolled in the community-based malaria study will be tested to serve as an age-matched HIV-uninfected control group for children tested in Aim 1. The level of measles antibodies will be compared between HIV-infected and uninfected children. For Aim 3, samples collected from participants in Aim 1 will be tested up to 4 years after treatment initiation. Long-term changes and trajectories of antibody levels over time will be compared across participants initiating treatment at different ages. The proposed studies will fill key gaps in our understanding of short and long-term immunity to measles virus among children living with HIV and initiating treatment before and after measles vaccination. The findings from the proposed studies will contribute to the scientific evidence on which to base recommendations for measles revaccination among children living with HIV in the era of early treatment initiation to ensure that children receive optimal care and remain protected from vaccine-preventable diseases.

项目摘要/摘要 估计有170万儿童在全球享有艾滋病毒，大约90％的撒哈拉 非洲。尽管抗逆转录病毒治疗，但其中许多儿童仍然容易受到疫苗预防的影响 疾病，包括麻疹。因此，世界卫生组织的战略咨询小组 专家（SAGE）在2015年建议的有关艾滋病毒和接受治疗的儿童建议 与麻疹重新捕获。近年来，随着婴儿期的较早诊断，艾滋病毒患儿童可能 现在，在9个月大时进行麻疹疫苗接种之前开始治疗。这种变化对 麻疹疫苗接种和对麻疹的长期免疫的相对时机尚未完全 已知。 Sage发现，没有足够的证据为开始的儿童提出建议 在麻疹疫苗接种之前的治疗并将其确定为研究的优先级。该提议将聚集在一起 一个机构和调查人员团队解决这一差距，并评估 针对赞比亚艾滋病毒患儿童麻疹抗体的早期治疗倡议。提议 研究与美国国家过敏和传染病研究所的优先事项保持一致 了解对传染病的免疫调查并培养国际科学合作。这 研究将在赞比亚南部农村的一个既定研究地进行，并将嵌套在两个 正在进行的研究：1）一项长期的队列研究，对艾滋病毒患儿童并在艾滋病毒诊所接受护理； 2）基于社区的疟疾研究。提出的研究将测试从 这些针对麻疹抗体解决研究问题的研究。对于目标1，样品收集了6-12 治疗后几个月将对5岁以下的儿童进行测试，并参加 小儿艾滋病毒队列。在参与者中，将比较麻疹抗体的水平 在不同的年龄（<9个月大，麻疹疫苗接种之前，9个月至1.9岁），2.0至2.0 4.9岁）。对于AIM 2，从参加社区疟疾研究的儿童中收集的样本 将测试以作为在AIM 1中测试的儿童的年龄匹配的HIV未感染的对照组。 在感染HIV的儿童和未感染的儿童之间，将比较麻疹抗体的抗体。对于AIM 3，样品 从AIM 1中收集的AIM 1的收集将在治疗计划后长达4年进行测试。长期变化 随着时间的推移，将在不同的参与者中比较抗体水平的轨迹 年龄。拟议的研究将填补我们对短期和长期免疫力的理解的关键空白 患有艾滋病毒的儿童的病毒并在麻疹疫苗接种前后开始治疗。发现 从拟议的研究中，将有助于科学证据，以此为基础建议 在早期治疗倡议时期，在艾滋病毒的儿童中发生麻疹，以确保 儿童获得最佳护理，并保护不受疫苗预防疾病的保护。