Early Infant Treatment

描述（由申请人提供）： 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长期存在潜伏感染细胞。我们提议在博茨瓦纳进行一项干预性研究，以筛查出生时的艾滋病毒感染情况，并为受感染的婴儿立即提供抗逆转录病毒治疗。开始 ART 后 24 个月时，未检测到病毒库的婴儿将接受受控治疗中断，并密切评估病毒反弹情况。我们将把 50 名 HIV 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 HIV，并在出生后 7 天以内开始 ART；20 名婴儿在出生后 72 小时内检测 HIV，但在出生后 42 天内检测 HIV，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；以及 ART 中断后功能性治愈的可能性（或病毒反弹的动态）。在博茨瓦纳，已建立的研究基础设施可以快速诊断艾滋病毒感染，并提高治疗依从性和随访率。在波士顿，可以进行专门的病毒学和免疫学测试来研究病毒库和早期治疗的免疫学影响。这种独特的合作将有助于详细研究如何通过早期 ART 启动来操纵细胞 HIV 储存库、免疫反应和病毒长期持续存在的机制。

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.