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: 10158923
• 负责人: Catherine Gayle Sutcliffe
• 金额: $ 21.04万
• 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 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158923
• 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

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 据估计，全球有170万儿童携带艾滋病毒，其中约90%在撒哈拉以南地区 非洲。尽管接受了抗逆转录病毒治疗，但这些儿童中的许多人仍然容易受到疫苗的影响，而疫苗是可以预防的 疾病，包括麻疹。因此，世界卫生组织的战略咨询小组 免疫接种专家(SAGE)在2015年建议，感染艾滋病毒并接受治疗的儿童 重新接种麻疹疫苗。近年来，由于在婴儿期被早期诊断，感染艾滋病毒的儿童可能 现在开始在9个月大的婴儿接种麻疹疫苗之前开始治疗。这一变化对中国的影响 麻疹疫苗接种和治疗的相对时机对麻疹短期和长期免疫的影响并不充分 为人所知。Sage发现，没有足够的证据为儿童提供建议 在接种麻疹疫苗之前进行治疗，并将其确定为研究优先事项。这项提议将使 一个由机构和调查人员组成的团队，以弥补这一差距，并评估 赞比亚艾滋病毒携带者儿童麻疹抗体的早期治疗。建议数 研究与国家过敏和传染病研究所的优先事项一致，以更好地 了解对传染病的免疫反应，并促进国际科学合作。这个 研究将在赞比亚南部农村的一个既定研究地点进行，并将嵌套在两个 正在进行的研究：1)对艾滋病毒携带者和在艾滋病毒诊所接受护理的儿童进行的长期队列研究； 2)一项基于社区的疟疾研究。拟议的研究将测试从以下地点收集的存储样本 这些针对麻疹抗体的研究解决了研究问题。对于目标1，6-12个样本收集 在开始治疗的几个月后，将从5岁以下的儿童开始测试，并参加 儿童艾滋病病毒队列。麻疹抗体水平将在开始治疗的参与者中进行比较。 在不同年龄(9个月龄和接种麻疹疫苗前、9个月至1.9岁和2.0岁至 4.9岁)。对于目标2，从社区疟疾研究中登记的儿童收集的样本 将作为目标1中测试的儿童的年龄匹配的未感染艾滋病毒的对照组。水平 将对感染艾滋病毒的儿童和未感染的儿童进行麻疹抗体水平的比较。目标3，样本 从AIM 1的参与者那里收集的数据将在治疗开始后长达4年进行测试。长期变化 并将比较在不同时间内开始治疗的参与者的抗体水平随时间的轨迹 年龄。拟议的研究将填补我们对麻疹短期和长期免疫的理解上的关键空白。 在感染艾滋病毒的儿童中传播病毒，并在接种麻疹疫苗前后开始治疗。调查结果 将有助于提供科学证据，作为建议的基础 在早期治疗开始的时代，对艾滋病毒携带者儿童进行麻疹复种，以确保 儿童得到最佳护理，并继续受到保护，免受疫苗可预防的疾病的侵袭。