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

婴儿护理点 HIV 检测和早期使用多替拉韦

• 批准号: 10696262
• 负责人: Roger L Shapiro
• 金额: $ 21.76万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696262
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Adverse event; Africa; Age; Binding; Birth; Botswana; Cessation of life; Child; Clinical; Country; Data; Databases; Diagnosis; Diagnostic; Diagnostic tests; Discipline of obstetrics; Dose; Enrollment; Goals; Guidelines; HIV; HIV Infections; HIV diagnosis; HIV-1; Health; Hospitalization; Human immunodeficiency virus test; Immunologics; Infant; Infection; International; Laboratories; Lamivudine; Life; Lopinavir/Ritonavir; Maternal-Fetal Transmission; Measures; Methodology; Modernization; Modification; Mothers; Nevirapine; New Agents; Newborn Infant; Outcome; Perinatal; Pharmaceutical Preparations; Positioning Attribute; Pregnant Women; Program Effectiveness; Program Research Project Grants; RNA; Recommendation; Regimen; Research; Research Design; Resource-limited setting; Site; Target Populations; Testing; Time; Treatment Failure; Treatment Protocols; Treatment outcome; Viral; Viral reservoir; Visit; Zidovudine; age group; antiretroviral therapy; barrier to testing; cohort; cost; diagnostic strategy; effectiveness evaluation; experience; high risk; high risk infant; implementation research; improved; in utero; infancy; infant outcome; neonate; novel therapeutics; point of care; point of care testing; program costs; programs; screening; treatment program; viral rebound

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.

项目摘要/摘要，床旁艾滋病毒检测和婴儿早期使用多鲁特韦（项目3） 在婴儿期延误艾滋病毒诊断和治疗的风险很高。婴儿发展为艾滋病， 死亡率高于任何其他年龄组，超过30%的死亡发生在生命的前42天。即使 婴儿开始治疗后，可用的治疗方案有限-目前的建议包括 药物，如奈韦拉平，齐多夫定，或洛匹那韦/利托那韦（LPV/r），很少用于成人-和治疗 失败是常见的。缺乏关于儿童使用新药剂的研究，导致不愿使用 新的代理商在指南中，即使他们批准用于婴儿。Dolutegravir（DTG）已被批准用于 婴儿从2020年6月出生30天，但尚未成为任何婴儿的一线治疗方案。 目前在非洲的ART项目。因此，迫切需要尽早开展执行研究， 在非洲国家治疗方案范围内，在婴儿出生时进行诊断，并开始使用现代 以DTG为基础的抗逆转录病毒治疗方案，尽可能早地为婴儿提供治疗。 在博茨瓦纳卫生和健康部以及P01计划的支持下，博茨瓦纳-哈佛大学 艾滋病研究所伙伴关系是独特的定位，开创了一个研究计划，以支持出生诊断， DTG治疗博茨瓦纳的婴儿。在早期婴儿治疗（EIT）研究的基础上， 我们将实施有针对性的出生检测（仅筛查感染艾滋病毒风险最高的暴露婴儿） 使用Cepheid Xpert平台进行基于机构的床旁（POC）检测。感染艾滋病毒的婴儿将接受治疗 立即，并被转诊入组一个队列，该队列在4周后过渡到基于DTG的ART。 并随访至少96周。通过与其他诊断方法以及 在EIT研究中接受基于LPV/r的ART，研究设计将使我们能够1）评估 增加低成本，有针对性的早期婴儿诊断博茨瓦纳国家治疗计划; 2）量化 在出生时被确定为艾滋病毒感染的儿童人数，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 和基于LPV/r的ART;以及4）比较基于DTG的 这项研究的结果将为希望实施出生诊断的项目提供信息， 早期婴儿治疗与DTG为基础的艺术，并将回答有关临床，病毒学， 以及早期DTG为基础的ART的免疫学影响。