Innovation across the spectrum of pediatric HIV care

项目摘要 在过去的十年里，抗逆转录病毒治疗(ART)的规模取得了显著的进步，但 对于210万儿童中的许多人来说，最佳的诊断、护理和治疗仍然有限 全球范围内由围产期感染的艾滋病毒。新的诊断技术和抗逆转录病毒药物(ARV)可以解决 这一治疗差距。然而，关键的问题仍然是利用这些创新的最有效方式 适用于资源非常有限的环境中的儿童。例如，计划应该如何最好地引入新的 婴儿艾滋病毒诊断的护理点检测，以及什么是最有效和最具成本效益的方法 推出儿科多洛替格韦和其他新兴的抗逆转录病毒药物？长期数据有限的地方，或传统临床 研究是不可行的，基于计算机的微观模拟建模可以使用现有的数据来指导决策 关于如何在有限的医疗预算下为感染艾滋病毒的儿童取得最佳结果。使用 NICHD R01支持(2014-2019年)，我们制定了预防艾滋病并发症的成本效益 (CEPAC)-儿科微模拟模型，并已得到世界卫生组织的知情指南和决定 世界卫生组织(WHO)、总统艾滋病紧急救援计划(PEPFAR)和 健康(Mohs)。在最初获奖周期的前4年，我们使用了微观模拟和成本- 发表17篇与儿科HIV预防、诊断和治疗相关的论文的效果分析方法 治疗。我们现在建议扩大这项工作的范围，扩大一个多学科团队， 在儿科艾滋病毒护理、研究、临床政策和成本效益方面的专业知识，并将津巴布韦加入 最初的重点是科特迪瓦和南非的国家。这将使我们能够比较三个国家的调查结果 PEPFAR环境，涵盖广泛和具有代表性的儿科艾滋病毒流行病学、临床 实践和医疗成本。我们还将开发新的基于模型的方法，包括位置优化 可供当地计划规划者用来检查新兴项目的模型和基于回归的元模型 儿科艾滋病毒护理的所有护理和治疗方法。我们提出了两个新的具体目标： 1.预测创新诊断技术在儿科的最佳位置和价值 艾滋病毒，包括用于婴儿艾滋病毒诊断的护理点化验。 2.评估实施新的抗逆转录病毒药物指南的最有效和最具成本效益的方法 为儿童推出新的抗逆转录病毒制剂，包括计划推出的多洛替格列韦。 这项提案的目标是帮助卫生部、世卫组织和 PEPFAR确定如何最佳利用稀缺资源来改善艾滋病毒感染儿童的长期健康状况。 继续和扩大对CEPAC-儿科建模计划的支持将使我们能够开发和 传播新的建模方法并解决关键的、特定于上下文的问题，这些问题涉及如何使 为全世界数百万受艾滋病毒影响的儿童最好地利用创新的新技术和治疗方法。

Project Summary The past decade has witnessed remarkable progress in the scale-up of antiretroviral therapy (ART), yet access to optimal diagnosis, care, and treatment remains limited for many of the 2.1 million children living with perinatally-acquired HIV worldwide. Novel diagnostic technologies and antiretroviral drugs (ARVs) can address this treatment gap. Critical questions remain, however, about the most effective way to utilize these innovations for children in settings with very limited resources. For example, how should programs best introduce new point-of-care assays for infant HIV diagnosis, and what are the most effective and cost-effective approaches to roll out pediatric dolutegravir and other emerging ARVs? Where long-term data are limited, or traditional clinical studies are not feasible, computer-based microsimulation modeling can use existing data to inform decisions about how to achieve the best outcomes for children with HIV under constrained healthcare budgets. With NICHD R01 support (2014-2019), we developed the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric microsimulation model and have informed guidelines and decisions from the World Health Organization (WHO), the President's Emergency Plan for AIDS Relief (PEPFAR), and country Ministries of Health (MOHs). In the first 4 years of the initial award cycle, we have used microsimulation and cost- effectiveness analysis methods to publish 17 papers related to pediatric HIV prevention, diagnosis, and treatment. We now propose to broaden the scope of this work, expanding a multidisciplinary team with diverse expertise in pediatric HIV care, research, clinical policy, and cost-effectiveness, and adding Zimbabwe to the original focus countries of Côte d'Ivoire and South Africa. This will allow us to compare findings across three PEPFAR settings that encompass a wide and representative range of pediatric HIV epidemiology, clinical practice, and healthcare costs. We will also develop new model-based methods, including location-optimization models and regression-based metamodels that can be used by local program planners to examine emerging care and treatment approaches across the spectrum of pediatric HIV care. We propose two new specific aims: 1. To project the optimal placement and value of innovative diagnostic technologies for pediatric HIV, including point-of-care assays for infant HIV diagnosis. 2. To evaluate the most effective and cost-effective ways to implement new ARV guidelines and introduce new ARV formulations for children, including the planned rollout of dolutegravir. The goal of this proposal is to help clinicians, program planners, and policymakers at MOHs, WHO, and PEPFAR identify the optimal use of scarce resources to improve long-term health for children with HIV. Continuation and expansion of support for the CEPAC-Pediatric modeling program will allow us to develop and disseminate novel modeling methods and address critical, context-specific questions about how to make the best use of innovative new technologies and treatments for millions of children affected by HIV worldwide.