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

描述(由申请人提供)：如果可以获得并以最佳方式使用，抗逆转录病毒疗法(ART)可以极大地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情况下，往往无法获得管理围产期艾滋病毒感染的最有效的诊断检测和抗逆转录病毒治疗方案。因此，仅在南非，每年就可能发生60,000多例围产期感染和20,000例儿童艾滋病毒死亡。南非的临床医生和政策制定者目前根据有限的关于疗效、毒性和成本的可用数据为儿童选择诊断测试和ART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策略的未来结果，来补充更传统的临床研究方法。本K01奖项申请基于这些方法提出了三个具体目标：1.构建围产期HIV疾病的蒙特卡罗模拟模型，并使用文献中和南非合作研究人员的最佳可用数据作为模型的参数。2.与延期治疗相比，评估出生第一年开始抗逆转录病毒治疗的长期临床结果和成本-效果。3.评价目前推荐用于婴儿早期诊断的诊断检测算法的临床结果和相对成本-效果。为了促进这项拟议的研究，候选人Andrea Ciaranello医学博士将在资源有限的情况下继续高级生物统计学和建模方法、运筹学和与艾滋病毒/艾滋病相关的伦理原则的课程研究。Ciaranello博士将受益于马萨诸塞州总医院和哈佛公共卫生学院的资源；拥有建模技术、围产期艾滋病毒感染和国际艾滋病毒研究专业知识并拥有杰出指导记录的导师的支持；以及她与南非临床研究人员和国际Kids‘ART-LINC研究联盟的合作。这一K01奖项将促进Ciaranello博士的职业发展，并帮助她过渡到一名独立的艾滋病毒临床结果调查员。相关性(见说明)：这一K01奖将产生分析，为有关儿童艾滋病毒感染管理的临床决策以及国家和国际政策指南提供信息。拟议的研究与国立卫生研究院艾滋病研究办公室公布的优先事项一致，包括评估最有效的、针对艾滋病毒感染儿童和青少年的诊断、护理和治疗的具体战略。

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.