Innovation across the spectrum of pediatric HIV care: Clinical impact and cost-effectiveness of long-acting antiretroviral therapy for breastfeeding people with HIV and their infants in Zimbabwe

儿科艾滋病毒护理领域的创新：长效抗逆转录病毒疗法对津巴布韦母乳喂养的艾滋病毒感染者及其婴儿的临床影响和成本效益

• 批准号: 10792976
• 负责人: Andrea Lynne Ciaranello
• 金额: $ 30.68万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10792976
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Address; Administrative Supplement; Adult; Affect; Anti-Retroviral Agents; Antiviral Agents; Award; Breast Feeding; Caring; Cessation of life; Child; Child Health; Childhood; Clinical; Clinical Trials; Collaborations; Costs and Benefits; Data; Development; Diagnosis; Drug Formulations; Effectiveness; Eligibility Determination; Ensure; Face; Formulation; Goals; Guidelines; HIV; HIV Infections; HIV diagnosis; Health; Health Policy; Health Services Accessibility; Human Milk; Human immunodeficiency virus test; Infant; Injectable; Integrase; Maternal Health; Methods; Mission; Modeling; Morbidity - disease rate; Mothers; National Institute of Child Health and Human Development; Oral; Outcome; Parents; Persons; Pharmaceutical Preparations; Policies; Policy Maker; Postpartum Period; Pregnancy; Prevention; Productivity; Public Health; Research; Research Design; Research Personnel; Risk; Risk Reduction; Technology; Testing; Time; United States National Institutes of Health; Viral; Viremia; Work; World Health Organization; Zimbabwe; antenatal care; antiretroviral therapy; caregiving; cost effective; cost effectiveness; economic impact; economic outcome; improved; infant infection; infection risk; inhibitor; innovation; models and simulation; new technology; novel; pediatric human immunodeficiency virus; postpartum outcome; pregnant; prevent; programs; scale up; testing services; therapy adherence; transmission process; treatment services

Project Summary Improved HIV testing and treatment in antenatal care have markedly increased viral suppression rates among pregnant and breastfeeding people with HIV (PWH) and reduced infant HIV infections. After delivery, however, PWH face unique barriers to ART adherence and are less likely to maintain viral suppression than non-postpartum adults. Viremia, in turn, increases risk of breastmilk HIV transmission to infants, which now accounts for more than half of the 150,000 annual infant HIV infections. Recent data have demonstrated the effectiveness of long-acting injectable ART (LA-ART) for PWH. This promising new technology may overcome challenges in ART adherence for postpartum PWH who are able to access care; this would prevent many infant infections and reduce morbidity and deaths among mothers and children. The World Health Organization (WHO) Pediatric Antiviral Drug Optimization (PADO) group has placed LA-ART formulations for prevention on their list of priority products for expedited development. Clinical trials of LA-ART in postpartum PWH are currently underway or in development by several NIH-supported trials networks. Since 2014, R01 HD079214 has supported the development of the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric microsimulation model of HIV prevention, diagnosis, and treatment in children. In Aim 2a of the current parent award (2019-2024), we are evaluating the clinical and economic impact of emerging antiretroviral drug formulations to improve the health of children affected by HIV. We first evaluated strategies for scaling up dolutegravir-based ART for children with HIV. This productive early work demonstrated that the next key questions in pediatric HIV will be focused on prevention. Together with newly emerging data on LA-ART for postpartum PWH, the current Administrative Supplement would allow us to leverage the work done in Aim 2a to address a new policy question currently being considered by NIH trials networks, WHO, and other guidelines-development agencies. We propose two Supplement Specific Aims: Aim A: To project the clinical outcomes and cost-effectiveness of long-acting injectable ART (LA-ART) offered to breastfeeding people with HIV in Zimbabwe. Aim B: To share findings with policymakers, inform emerging guidelines, and guide future research. This analysis, part of Aim 2a, is eligible for an Administrative Supplement according to NICHD criteria: 1) “to address special, time-critical cases such as countering a major threat to public health or taking advantage of … unanticipated opportunities to increase the value of the project consistent with the originally approved objectives,” and 2) “to prepare and disseminate materials …. ensuring that important findings from the project are made widely available in a timely and effective manner.” Support from this supplement will allow us to address a critical, new, time-sensitive question related to the parent R01 objectives: evaluating the clinical and economic impact of novel antiretroviral formulations for children affected by HIV.

项目摘要 改进的艾滋病毒检测和产前护理治疗显著提高了病毒抑制率 在孕妇和哺乳期感染艾滋病毒(PWH)的人中，减少婴儿艾滋病毒感染。在分娩之后， 然而，与抗逆转录病毒治疗相比，pwh面临着独特的抗逆转录病毒治疗障碍，不太可能保持病毒抑制。 非产后成人。病毒血症反过来增加了母乳传播艾滋病毒给婴儿的风险，现在 占每年15万婴儿艾滋病毒感染人数的一半以上。最近的数据表明， 长效可注射ART(LA-ART)治疗PWH的疗效。这项前景看好的新技术可能会克服 能够获得护理的产后PWH患者在坚持抗逆转录病毒治疗方面面临的挑战；这将阻止许多 减少婴儿感染，减少母亲和儿童的发病率和死亡率。世界卫生组织 (世卫组织)儿科抗病毒药物优化(PADO)小组已将LA-ART配方用于预防 他们加快发展的优先产品清单。LA-ART治疗产后PWH的临床试验如下 NIH支持的几个试验网络目前正在进行或正在开发中。 自2014年以来，R01 HD079214一直支持制定预防艾滋病的成本效益 并发症(CEPAC)-#年艾滋病毒预防、诊断和治疗的儿科微模拟模型 孩子们。在当前家长奖(2019-2024)的目标2a中，我们正在评估临床和经济 新出现的抗逆转录病毒药物配方对改善受艾滋病毒影响儿童的健康的影响。我们首先 评估了扩大基于多洛替格列韦的抗逆转录病毒药物治疗艾滋病毒儿童的战略。这项富有成效的早期工作 表明儿科艾滋病毒的下一个关键问题将集中在预防上。与新近一起 关于产后PWH的LA-ART的新数据，目前的行政补充将允许我们 利用在目标2a中所做的工作来解决NIH试验目前正在考虑的一个新的政策问题 网络、世卫组织和其他指导方针--发展机构。我们提出两个补编的具体目标： 目的A：预测长效可注射抗逆转录病毒治疗(LA-ART)的临床结果和成本-效果 向津巴布韦的艾滋病毒携带者提供母乳喂养。 目标B：与政策制定者分享研究结果，告知新出现的指导方针，并指导未来的研究。 这项分析是目标2a的一部分，根据《消除对妇女一切形式歧视公约》的标准，有资格获得行政补编：1) 解决特殊的时间关键型案例，例如应对对公共卫生的重大威胁或利用… 与最初批准的项目一致地增加项目价值的意想不到的机会 目标，“和2)”准备和传播材料…。确保项目的重要发现 以及时和有效的方式广泛提供。本增刊的支持将使我们能够 解决与母公司R01目标相关的关键、新的、时间敏感的问题：评估临床和 新型抗逆转录病毒制剂对感染艾滋病毒儿童的经济影响。

项目成果

Prevalence of undiagnosed HIV among children in South Africa, Côte d'Ivoire and Zimbabwe: a model-based analysis to inform paediatric HIV screening programmes.

• DOI: 10.1002/jia2.26045
• 发表时间: 2022-12
• 期刊: Journal of the International AIDS Society
• 影响因子: 6

Increasing the initiation of antiretroviral therapy through optimal placement of diagnostic technologies for pediatric HIV in Zimbabwe: A modeling analysis.

• DOI: 10.1016/j.ijid.2023.05.013
• 发表时间: 2023-09
• 期刊: INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
• 影响因子: 8.4
• 作者: Yildirim, Melike;Webb, Karen A.;Ciaranello, Andrea L.;Amick, Alyssa K.;Mushavi, Angela;Chimwaza, Anesu;Claypool, Anneke;Murape, Tendayi;McCann, Nicole C.;Flanagan, Clare F.;Jalali, Mohammad S.
• 通讯作者: Jalali, Mohammad S.

Evaluating Point-of-Care Nucleic Acid Tests in Adult Human Immunodeficiency Virus Diagnostic Strategies: A Côte d'Ivoire Modeling Analysis.

• DOI: 10.1093/ofid/ofab225
• 发表时间: 2021-06
• 期刊: Open forum infectious diseases
• 影响因子: 4.2
• 作者: Neilan AM;Cohn J;Sacks E;Gandhi AR;Fassinou P;Walensky RP;Kouadio MN;Freedberg KA;Ciaranello AL
• 通讯作者: Ciaranello AL

Do not forget the children: a model-based analysis on the potential impact of COVID-19-associated interruptions in paediatric HIV prevention and care.

• DOI: 10.1002/jia2.25864
• 发表时间: 2022-01
• 期刊: Journal of the International AIDS Society
• 影响因子: 6
• 作者: Flanagan CF;McCann N;Stover J;Freedberg KA;Ciaranello AL
• 通讯作者: Ciaranello AL

Cost-effectiveness of point-of-care versus centralised, laboratory-based nucleic acid testing for diagnosis of HIV in infants: a systematic review of modelling studies.

• DOI: 10.1016/s2352-3018(23)00029-2
• 发表时间: 2023-05
• 期刊: LANCET HIV
• 影响因子: 16.1
• 作者: le Roux, Stanzi M.;Odayar, Jasantha;Sutcliffe, Catherine G.;Salvatore, Phillip P.;de Broucker, Gatien;Dowdy, David;McCann, Nicole C.;Frank, Simone C.;Ciaranello, Andrea L.;Myer, Landon;Vojnov, Lara
• 通讯作者: Vojnov, Lara