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

当抗逆转录病毒疗法（ART）可用并得到最佳使用时，可以显著降低发病率。 和围产期获得性艾滋病相关的死亡率。在资源有限的环境中，如南 然而，非洲是管理围产期艾滋病毒最有效的诊断检测和抗逆转录病毒疗法的国家。 感染常常不可用。结果，超过60，000例围产期感染和20，000例儿童艾滋病毒感染 每年仅在南非就可能发生死亡。 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， 根据关于疗效、毒性和成本的有限可用数据，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， 艾滋病毒感染儿童一生中诊断和治疗策略的未来结果。 K 01奖的申请基于这些方法提出了三个具体目标： 1.建立围产期HIV感染的MonteCarlo模拟模型，并将其作为模型参数， 该模型采用了文献中和南非合作研究人员提供的最佳数据。 2.评估在第一年开始ART的长期临床结果和成本效益。 与延迟治疗相比， 3.评价目前推荐的诊断性化疗的临床结局和相对成本效益， 用于婴儿早期诊断的测试算法。 为了促进这项拟议的研究，候选人，安德烈Ciaranello，医学博士，将追求课程， 先进的生物统计学和建模方法，运筹学，以及相关的伦理原则， 在资源有限的情况下防治艾滋病毒/艾滋病。西拉内洛博士将受益于马萨诸塞州的资源 总医院和哈佛公共卫生学院;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，并与杰出的记录， 导师;以及她与南非临床研究人员和国际 儿童艺术-LINC研究联盟。这个K 01奖将促进Ciaranello博士的职业发展， 她转变为一名独立的艾滋病毒临床结果调查员。 相关性（参见说明）： 该K 01奖将导致分析，将告知临床决策，以及国家和国际 关于儿童艾滋病毒感染管理的政策指导方针。拟议的研究符合 国家卫生研究院艾滋病研究办公室公布的优先事项，包括评估最有效的， 为感染艾滋病毒的儿童和青少年的诊断、护理和治疗制定具体战略。

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.