Early Infant Treatment

婴儿早期治疗

• 批准号: 9084461
• 负责人: Daniel R. Kuritzkes
• 金额: $ 98万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9084461
• 关键词: Address; Adult; Adverse event; Affect; Age; Anti-Retroviral Agents; Birth; Boston; Botswana; CD4 Positive T Lymphocytes; Cells; Clinic; Clinical Trials; Collaborations; Control Groups; Cytometry; DNA; Data; Detection; Development; Devices; Drug Kinetics; Early treatment; Enrollment; Ethics; Evaluation; HIV; HIV Infections; HIV-1; Health; Hour; Human immunodeficiency virus test; Immune; Immune response; Immune system; Immunologic Tests; Immunologics; Infant; Infection; Interruption; Intervention Studies; Investigation; Kinetics; Lead; Life; Mass Spectrum Analysis; Measures; Memory; Monitor; Outcome; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Plasma; Population; Prenatal Diagnosis; RNA; Research Infrastructure; Safety; Sampling; Shapes; Site; Sorting - Cell Movement; Staging; Stem cells; T-Lymphocyte Subsets; Testing; Time; Viral; Viral reservoir; Viremia; adaptive immunity; antiretroviral therapy; base; cohort; computer studies; experience; follow-up; immune activation; infancy; memory CD4 T lymphocyte; neonate; novel; postnatal; prevent; prospective; rapid diagnosis; treatment adherence; ward

DESCRIPTION (provided by applicant): Combination antiretroviral treatment (ART) initiated shortly after HIV infection may prevent seeding of a long-lasting reservoir of latently infected cells in some infants. We propose an interventional study in Botswana to screen for HIV infection from birth and provide immediate ART to infected infants. At 24 months from ART initiation, infants without viral reservoir detection will undergo a controlled treatment interrupton with close evaluation for viral rebound. We will enroll 50 HIV+ infants into two parallel early treatment cohorts: 30 infants who test HIV+ within 72 hours of birth and initiate ART at < 7 days of life, and 20 infants who test HIV- within 72 hours of birth but HIV+ within 42 days of life and initiate ART by 56 days of life. Primary study aims will evaluate safety and efficacy of early ART; virologic and immunologic outcomes with early ART; and the possibility of functional cure (or the dynamics of viral rebound) after ART interruption. In Botswana, an established research infrastructure allows rapid diagnosis of HIV infection and high rates of treatment adherence and follow-up. In Boston, specialized virologic and immunologic testing is available to study viral reservoirs and the immunologic impact of early treatment. This unique collaboration will allow for a detailed investigation of how cellular HIV reservoirs, immune responses, and mechanisms of viral long-term persistence can be manipulated through early ART initiation.

描述（由申请人提供）：在HIV感染后不久开始的联合抗逆转录病毒治疗（ART）可能会阻止某些婴儿体内潜伏感染细胞的长期储存。我们建议在博茨瓦纳进行一项干预性研究，从出生开始筛查艾滋病毒感染，并为感染的婴儿提供立即的抗逆转录病毒治疗。在ART开始后24个月，未检测到病毒储库的婴儿将接受受控的治疗中断，并密切评估病毒反弹。我们将50名HIV阳性婴儿纳入两个平行的早期治疗队列：30名婴儿在出生后72小时内检测出HIV阳性，并在出生后< 7天开始ART，20名婴儿在出生后72小时内检测出HIV-，但在出生后42天内检测出HIV阳性，并在出生后56天开始ART。主要研究目的是评估早期ART的安全性和有效性; 早期ART的病毒学和免疫学结果; ART中断后功能性治愈的可能性（或病毒反弹的动力学）。在博茨瓦纳，现有的研究基础设施可以迅速诊断艾滋病毒感染，坚持治疗和后续行动的比率很高。在波士顿，专门的病毒学和免疫学检测可用于研究病毒储库和早期治疗的免疫学影响。这种独特的合作将允许详细调查如何通过早期ART启动来操纵细胞HIV储库，免疫反应和病毒长期持久性机制。