Optimizing Outcomes for HIV-Exposed and HIV-Infected Children in South Africa

描述（由申请人提供）：抗逆转录病毒疗法（ART）可以显著降低与围产期获得性艾滋病毒疾病相关的发病率和死亡率。然而，在南非等资源有限的环境中，往往没有最有效的诊断测试和治疗围产期艾滋病毒感染的抗逆转录病毒治疗方案。因此，仅在南非，每年就可能发生6万多例围产期感染和2万多例儿科艾滋病毒死亡。南非的临床医生和决策者目前根据有限的关于疗效、毒性和成本的现有数据为儿童选择诊断测试和抗逆转录病毒治疗方案。决策分析可以通过综合来自多个来源的数据并预测感染艾滋病毒儿童一生中诊断和治疗战略的未来结果，从而补充更传统的临床研究方法。本次K01奖申请基于这些方法提出了三个具体目标：构建围产期HIV疾病的蒙特卡罗模拟模型，并使用文献和南非合作研究者的最佳可用数据作为模型参数。评估在生命第一年开始抗逆转录病毒治疗与推迟治疗的长期临床结果和成本效益。3. 评估目前推荐的用于婴儿早期诊断的诊断测试算法的临床结果和相对成本效益。为了促进这项拟议的研究，候选人Andrea Ciaranello博士将学习高级生物统计学和建模方法、运筹学和资源有限环境下与艾滋病毒/艾滋病相关的伦理原则等课程。Ciaranello博士将受益于马萨诸塞州总医院和哈佛大学公共卫生学院的资源；获得在建模技术、围产期艾滋病毒感染和国际艾滋病毒研究方面具有专业知识的导师的支持，并具有杰出的指导记录；以及她与南非临床研究人员和国际儿童ART-LINC研究联盟的合作。这个K01奖将促进Ciaranello博士的职业发展和她过渡到一个独立的HIV临床结果研究者。相关性（见说明）：这一K01奖将导致分析，为临床决策以及国家和国际政策指南提供有关儿童艾滋病毒感染管理的信息。拟议的研究与美国国立卫生研究院艾滋病研究办公室公布的优先事项一致，包括对感染艾滋病毒的儿童和青少年的诊断、护理和治疗的最有效、具体设定的战略进行评估。

DESCRIPTION (provided by applicant): When available and used optimally, antiretroviral therapy (ART) can dramatically reduce the morbidity and mortality associated with perinatally-acquired HIV disease. In resource-limited settings such as South Africa, however, the most effective diagnostic tests and ART regimens for the management of perinatal HIV infection are often not available. As a result, more than 60,000 perinatal infections and 20,000 pediatric HIV deaths may occur annually in South Africa alone. Clinicians and policy-makers in South Africa currently select diagnostic tests and ART regimens for children based on limited available data about efficacy, toxicity, and cost. Decision analysis can complement more traditional clinical research methods by synthesizing data from multiple sources and projecting the future outcomes of diagnostic and therapeutic strategies over the lifetimes of HIV-infected children. This K01 award application proposes three Specific Aims based on these methods: 1. To construct a Monte Carlo simulation model of perinatal HIV disease, and to use as parameters in the model the best available data in the literature and from collaborating investigators in South Africa. 2. To evaluate the long-term clinical outcomes and cost-effectiveness of ART initiation in the first year of life compared to deferred therapy. 3. To evaluate the clinical outcomes and relative cost-effectiveness of currently recommended diagnostic testing algorithms for early infant diagnosis. To facilitate this proposed research, the Candidate, Andrea Ciaranello, MD, will pursue coursework in advanced biostatistics and modeling methodology, operations research, and ethical principles pertinent to HIV/AIDS in resource-limited settings. Dr. Ciaranello will benefit from the resources of the Massachusetts General Hospital and the Harvard School of Public Health; from the support of mentors with expertise in modeling techniques, perinatal HIV infection, and international HIV research and with outstanding records of mentorship; and from her collaborations with clinical investigators in South Africa and with the international Kids' ART-LINC research consortium. This K01 Award will facilitate Dr. Ciaranello's career development and her transition to an independent HIV clinical outcomes investigator. RELEVANCE (See instructions): This K01 Award will lead to analyses that will inform clinical decisions, as well as national and international policy guidelines, regarding the management of HIV infection in children. The proposed research aligns with the published priorities of the NIH Office of AIDS research, including the evaluation of the most effective, setting-specific strategies for diagnosis, care and treatment of HIV-infected children and adolescents.