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艾滋病毒感染者儿童中的分析性治疗中断:EPIICAL 联盟的立场声明。

Analytical treatment interruption in children living with HIV: position statement from the EPIICAL consortium.

机构信息

Gertrude H Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA.

Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg Academic Hospital, Cape Town, South Africa.

出版信息

Lancet HIV. 2024 Oct;11(10):e700-e710. doi: 10.1016/S2352-3018(24)00157-7. Epub 2024 Jul 23.

Abstract

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions.

摘要

分析性治疗中断(ATI)被广泛认为是深入了解 HIV 治愈方法的研究的重要组成部分,但讨论主要集中在成年人身上。为了弥补这一空白,我们回顾了与儿科人群中 ATI 的安全性和实用性相关的证据。已经进行了三项使用 CD4 T 细胞和临床标准来指导抗逆转录病毒治疗(ART)重启的随机 ATI 试验。这些试验发现 ATI 在儿童中风险较低,包括与神经认知结果相关的令人安心的发现。与急性感染期间接受治疗的成年人类似,在生命早期接受治疗的婴儿的病毒学和免疫学参数发生变化,增加了他们实现无 ART 病毒控制的可能性。早期 ART 限制了病毒库的大小和多样性,并塑造了有效的先天和 HIV 特异性体液和细胞反应。已经有报道称,在早期接受治疗的儿童中,有几例可持久控制无 ART 的病毒。我们建议,在适当的情况下,并且在有足够监测的情况下,ATI 应纳入无 ART 病毒控制研究中,以研究与 HIV 共存的儿童。儿科参与者最有可能受益,并且最有可能有前瞻性地实现这些受益的时间。将儿童排除在 ATI 试验之外会限制证据基础,并延迟干预措施的获得。

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