Point-of-Care HIV Testing and Early Dolutegravir Use for Infants

项目摘要/摘要，婴儿艾滋病毒检测和早期使用多洛替格列韦(项目3) 在婴儿时期推迟艾滋病毒诊断和治疗的风险很高。婴儿发展为艾滋病并死于 死亡率比任何其他年龄段都高，30%以上的死亡发生在生命的前42天。即使是在 开始对婴儿进行治疗，可用的治疗方案有限--目前的建议包括 成人很少使用的药物，如奈韦拉平、齐多夫定或洛皮那韦/利托那韦(LPV/r)，以及治疗 失败是很常见的。缺乏对儿童使用新制剂的研究，导致不愿使用 较新的药物即使在批准用于婴儿的指南中也是如此。多洛替格雷(DTG)被批准用于 婴儿从2020年6月出生30天起，但一直没有成为任何一种婴儿的一线治疗方案 目前在非洲的艺术项目。因此，迫切需要尽早开展实施研究。 在非洲的国民治疗方案中对出生时的婴儿进行诊断，并开始使用现代 以DTG为基础的抗逆转录病毒治疗方案应尽可能早地用于婴幼儿。 在博茨瓦纳卫生和福利部和这一P01计划的支持下，博茨瓦纳-哈佛 艾滋病研究所伙伴关系处于独特的地位，可以开创一项支持出生诊断和治疗的研究计划 博茨瓦纳婴儿的DTG治疗。基于早期婴儿治疗(EIT)研究中的先前研究， 我们将实施有针对性的出生检测(只筛查感染艾滋病毒风险最高的暴露婴儿) 使用Cepheid Xpert平台进行基于设施的护理点(POC)测试。感染艾滋病毒的婴儿将得到治疗 立即，并被推荐登记到队列中，该队列在四周后过渡到基于DTG的ART 生命，并随访了至少96周。与其他诊断方法和儿童进行比较 在EIT研究中收到基于LPV/r的ART，研究设计将使我们能够1)评估 在博茨瓦纳国民治疗计划中增加低成本、有针对性的早期婴儿诊断；2)量化 出生时被确认为艾滋病毒感染者的儿童数量，并确定从诊断到开始抗逆转录病毒治疗的时间 部署POC测试；3)比较基于DTG的抑制和12周抑制所需的时间 和基于LPV/r的ART；以及4)比较DTG和DTG的96周结局和总体病毒抑制 和基于LPV/R的ART。这项研究的结果将为希望实施出生诊断和 使用基于DTG的ART进行婴儿早期治疗，并将回答有关临床、病毒学、 以及早期基于DTG的抗逆转录病毒治疗对免疫学的影响。

Project Summary/Abstract, Point-of-Care HIV Testing and Early Dolutegravir Use for Infants (Project 3) The stakes of delaying HIV diagnosis and treatment in infancy are high. Infants progress to AIDS and die at a higher rate than any other age group, with over 30% of deaths occurring in the first 42 days of life. Even when treatment is started for infants, the available treatment regimens are limited – current recommendations include drugs such as nevirapine, zidovudine, or lopinavir/ritonavir (LPV/r) that are rarely used in adults – and treatment failure is common. Studies on the use of newer agents in children are lacking, leading to a reluctance to use newer agents in guidelines even after their approval for infants. Dolutegravir (DTG) was approved for use in infants from 30 days of life in June 2020, but has not become the first-line treatment regimen for infants in any current ART program in Africa. There is therefore an urgent need for implementation research to embed early infant diagnostics at the time of birth within national treatment programs in Africa, and to begin using modern DTG-based ART regimens for infants from as early in life as possible. With the support of Botswana's Ministry of Health and Wellness and this P01 program, the Botswana–Harvard AIDS Institute Partnership is uniquely positioned to pioneer a research program to support birth diagnosis and DTG treatment for infants in Botswana. Building on prior research within the Early Infant Treatment (EIT) Study, we will implement targeted birth testing (screening only exposed infants with the highest risk of HIV acquisition) by facility-based point-of-care (POC) testing with the Cepheid Xpert platform. Infants with HIV will be treated immediately, and referred for enrollment into a cohort that is transitioned to DTG-based ART at four weeks of life and followed for at least 96 weeks. With comparisons to alternate diagnostic approaches and to children who received LPV/r-based ART within the EIT Study, the study design will allow us to 1) evaluate the feasibility of adding low-cost, targeted early infant diagnosis to the Botswana national treatment program; 2) quantify the number of children identified as HIV infected at birth and determine time from diagnosis to ART initiation when POC testing is deployed; 3) compare the time to suppression and 12-week suppression between DTG-based and LPV/r-based ART; and 4) compare 96-week outcomes and overall viral suppression between DTG-based and LPV/r-based ART. Results from this study will inform programs that wish to implement birth diagnostics and early infant treatment with DTG-based ART, and will answer critical questions regarding the clinical, virologic, and immunologic impact of early DTG-based ART.