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

当抗逆转录病毒疗法(ART)可用并以最佳方式使用时，可显著降低发病率。 以及与围产期获得性艾滋病毒疾病相关的死亡率。在资源有限的环境中，如南方 然而，非洲是管理围产期艾滋病毒的最有效的诊断测试和ART方案 感染通常是不可用的。因此，60,000多名围产期感染和20,000名儿童艾滋病毒 仅在南非每年就可能发生死亡事件。 南非的临床医生和政策制定者目前选择诊断测试和ART方案 基于有限的关于疗效、毒性和成本的可用数据。决策分析可以补充 更传统的临床研究方法，通过综合来自多个来源的数据并将 艾滋病毒感染儿童一生中诊断和治疗策略的未来结果。 根据这些方法，本K01奖项的申请提出了三个具体目标： 1.建立围产期HIV感染的蒙特卡罗模拟模型，并将其作为围产期HIV感染的参数 该模型是文献和南非合作研究人员提供的最佳可用数据。 2.评估第一年开展抗逆转录病毒治疗的长期临床结果和成本效益 生命，与延期治疗相比。 3.评估目前推荐的诊断方法的临床结果和相对成本效益 测试用于婴儿早期诊断的算法。 为了促进这项拟议的研究，候选人Andrea Ciaranello，医学博士，将在 先进的生物统计和建模方法、运筹学和伦理原则 在资源有限的情况下防治艾滋病毒/艾滋病。Ciaranello博士将从马萨诸塞州的资源中受益 综合医院和哈佛大学公共卫生学院；来自具有以下专业知识的导师的支持 建模技术、围产期艾滋病毒感染和国际艾滋病毒研究，并拥有杰出的记录 指导；以及她与南非临床研究人员和国际社会的合作 儿童艺术-LINC研究联盟。这一K01奖将促进Ciaranello博士的职业发展和 她转变为一名独立的艾滋病毒临床结果调查员。 相关性(请参阅说明)： 这一K01奖将导致为临床决策以及国内和国际提供信息的分析 关于儿童艾滋病毒感染管理的政策指导方针。这项拟议的研究与 美国国立卫生研究院艾滋病研究办公室公布的优先事项，包括对最有效、 制定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。

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.