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.

项目概要/摘要 全球估计有 170 万儿童感染艾滋病毒，其中约 90% 生活在撒哈拉以南地区 非洲，尽管接受了抗逆转录病毒治疗，但其中许多儿童仍然容易受到疫苗可预防的影响。 世界卫生组织战略咨询小组对包括麻疹在内的疾病进行了检查。 免疫专家 (SAGE) 在 2015 年建议感染艾滋病毒并接受治疗的儿童 近年来，随着婴儿期早期诊断，感染艾滋病毒的儿童可能会重新接种麻疹疫苗。 现在应在 9 个月大时开始接种麻疹疫苗。 这种变化的影响。 麻疹疫苗接种和治疗的相对时机对麻疹短期和长期免疫力的影响尚不完全 SAGE 发现没有足够的证据为开始的儿童提出建议。 麻疹疫苗接种前的治疗，并将其确定为研究重点。 一个由机构和研究人员组成的团队来解决这一差距并评估短期和长期影响 赞比亚艾滋病毒感染儿童的麻疹抗体早期治疗启动。 研究与国家过敏和传染病研究所的优先事项保持一致，以更好地 了解对传染病的免疫反应并促进国际科学合作。 研究将在赞比亚南部农村的一个既定研究地点进行，并将嵌套在两个研究中心内 正在进行的研究：1）一项针对感染艾滋病毒并在艾滋病毒诊所接受护理的儿童的长期队列研究； 2) 一项基于社区的疟疾研究将测试从其中收集的储存样本。 这些针对麻疹抗体的研究解决了针对目标 1 的研究问题，收集了 6-12 个样本。 治疗开始后几个月将对 5 岁以下的儿童进行测试，并入组 将比较开始治疗的参与者的麻疹抗体水平。 不同年龄（<9 个月大且接种麻疹疫苗之前、9 个月至 1.9 岁、2.0 至 2.0 岁） 4.9 岁）对于目标 2，从参加社区疟疾研究的儿童中采集样本。 将接受测试，作为目标 1 中测试的儿童的年龄匹配的未感染 HIV 的对照组。 对于目标 3，将比较感染艾滋病毒和未感染艾滋病毒的儿童样本中的麻疹抗体。 从目标 1 的参与者收集的数据将在治疗开始后 4 年内进行长期变化。 将比较在不同时间开始治疗的参与者之间的抗体水平随时间的变化轨迹 拟议的研究将填补我们对麻疹短期和长期免疫力理解的关键空白。 感染艾滋病毒的儿童中的病毒并在接种麻疹疫苗之前和之后开始治疗。 拟议的研究将有助于提供科学证据，作为建议的基础 在早期治疗开始时对感染艾滋病毒的儿童重新接种麻疹疫苗，以确保 儿童得到最佳护理并免受疫苗可预防疾病的影响。