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: 10495250
• 负责人: Roger L Shapiro
• 金额: $ 27.07万
• 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/10495250
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Adverse event; Africa; 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; Institutes; 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; base; 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、护理点 HIV 检测和婴儿早期使用多替拉韦（项目 3） 在婴儿期延迟艾滋病毒诊断和治疗的风险很高，婴儿会发展为艾滋病并很快死亡。 死亡率高于任何其他年龄组，超过 30% 的死亡发生在出生后 42 天内。 婴儿已开始治疗，可用的治疗方案有限——目前的建议包括 例如很少用于成人的奈韦拉平药物、齐多夫定或洛匹那韦/利托那韦 (LPV/r) – 以及治疗 缺乏对儿童使用新药物的研究，导致不愿意使用。 即使在多替拉韦（DTG）被批准用于婴儿后，指南中仍出现了新的药物。 2020年6月开始对出生后30天的婴儿进行治疗，但尚未成为任何婴儿的一线治疗方案 因此，非洲当前的 ART 计划迫切需要尽早实施实施研究。 在非洲国家治疗计划中对婴儿出生时进行诊断，并开始使用现代技术 尽早为婴儿提供基于 DTG 的 ART 治疗方案。 在博茨瓦纳卫生和保健部以及本 P01 计划的支持下，博茨瓦纳-哈佛 艾滋病研究所合作伙伴关系具有独特的地位，可以开拓支持出生诊断和治疗的研究计划 博茨瓦纳的婴儿 DTG 治疗以早期婴儿治疗 (EIT) 研究中的先前研究为基础， 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） 通过使用 Cepheid Xpert 平台进行基于设施的护理点 (POC) 检测，感染艾滋病毒的婴儿将得到治疗。 立即，并被转介入一个队列，该队列在第 4 周时过渡到基于 DTG 的 ART 生命并跟踪至少 96 周，与其他诊断方法和儿童进行比较。 在 EIT 研究中接受基于 LPV/r 的 ART，研究设计将使我们能够 1) 评估可行性 将低成本、有针对性的早期婴儿诊断纳入博茨瓦纳国家治疗计划 2) 量化 确定出生时感染 HIV 的儿童数量，并确定从诊断到开始 ART 的时间 部署 POC 测试；3）比较基于 DTG 的抑制时间和 12 周抑制时间 和基于 LPV/r 的 ART；4) 比较基于 DTG 的 96 周结果和总体病毒抑制 这项研究的结果将为希望实施出生诊断和治疗的项目提供信息。 使用基于 DTG 的 ART 进行早期婴儿治疗，并将回答有关临床、病毒学、 以及早期基于 DTG 的 ART 的免疫学影响。