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

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.

项目总结/摘要 据估计，全球有170万儿童感染艾滋病毒，其中约90%在撒哈拉以南地区。 非洲尽管进行了抗逆转录病毒治疗，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，世界卫生组织战略咨询小组 免疫专家（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，随着婴儿期早期诊断，感染艾滋病毒的儿童可能 现在，在9个月大时接种麻疹疫苗之前开始治疗。这一变化的影响， 麻疹疫苗接种和治疗的相对时间对麻疹的短期和长期免疫力不完全 知道的SAGE发现，没有足够的证据为那些开始 麻疹疫苗接种前的治疗，并将其确定为研究优先事项。这项提案将汇集 一个由机构和调查人员组成的小组，以解决这一差距，并评估短期和长期影响， 赞比亚感染艾滋病毒儿童的麻疹抗体早期治疗启动。拟议 研究与国家过敏和传染病研究所的优先事项相一致， 了解对传染病的免疫反应，促进国际科学合作。的 研究将在赞比亚南部农村的一个既定研究地点进行，并将在两个 正在进行的研究：1）对感染艾滋病毒并在艾滋病毒诊所接受治疗的儿童进行的长期队列研究; （2）以社区为基础的疟疾研究。拟议的研究将测试从以下地点收集的储存样本： 这些研究为麻疹抗体的研究解决了问题。对于目标1，收集了6-12份样品 治疗开始后3个月，将对5岁以下儿童进行检测，并入组 儿科艾滋病毒队列。将比较开始治疗的参与者的麻疹抗体水平 在不同年龄（<9个月和麻疹疫苗接种前，9个月至1.9岁，2.0至2.5岁）， 4.9年龄）。对于目标2，从参加社区疟疾研究的儿童中收集样本， 将作为目标1中检测的儿童的年龄匹配的未感染艾滋病毒的对照组进行检测。水平 将比较感染艾滋病毒和未感染艾滋病毒儿童的麻疹抗体水平。对于目标3，样品 从目标1的受试者中收集的样本将在治疗开始后长达4年进行检测。长期变化 抗体水平随时间的轨迹将在不同时间开始治疗的参与者之间进行比较。 年龄拟议中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 在麻疹疫苗接种前后，为感染艾滋病毒的儿童接种麻疹疫苗并开始治疗。这些发现 将有助于提供科学证据，作为提出建议的基础。 在早期治疗开始的时代，对感染艾滋病毒的儿童进行麻疹疫苗再接种，以确保 儿童得到最佳护理，并继续免受疫苗可预防疾病的侵害。