Improving prevention of mother-to-child HIV transmission outcomes in Malawi

描述(申请人提供)：2010年，估计有250,000名儿童死于艾滋病，2011年有超过330,000名儿童新感染艾滋病毒，其中大部分在撒哈拉以南非洲。有了目前有效、低成本的预防艾滋病毒母婴传播(母婴传播)的医疗干预措施，这些感染大多是可以预防的。与艾滋病有关的儿童死亡率居高不下表明，需要进行科学严谨的执行研究，以便在资源有限的情况下成功实施循证干预措施，如防止母婴传播。贝勒医学院(BCM)反病毒学和全球卫生科助理教授Maria Kim博士致力于通过学习如何识别、研究和解决执行问题，缩小知识和行动之间的差距，从而改善有需要的妇女和儿童获得和使用干预措施的机会。Kim博士的研究将评估如何优化马拉维新的国家防止母婴传播方案选项B+(B+)的实施。其他预防母婴传播方法要求根据临床或实验室标准对艾滋病毒疾病进行分期，以区分为自身健康需要终身治疗的妇女和仅需要短期药物治疗的预防母婴传播妇女。相比之下，B+为所有感染艾滋病毒的孕妇和哺乳期妇女提供终身抗逆转录病毒治疗。因此，从理论上讲，B+提供了一种简化的方法，可以改善吸收、保留和传播结果。然而，目前还没有发表过评估其疗效的研究。《柳叶刀》最近的一篇评论强调，在其他国家广泛实施B+之前，迫切需要更多关于B+的数据。作为马拉维的一名儿科医生，Kim博士参与了一项研究，该研究表明，母婴艾滋病毒服务的不充分协调是导致预防母婴传播治疗70%失访的重要原因。基于这些数据，她开始了一项前瞻性的开放队列研究，以检查一种名为Tingathe的策略的影响，该策略利用社区卫生工作者(CHW)帮助妇女通过预防母婴传播治疗。2011年，金博士分析了1600对母婴配对的两年数据，这些数据表明母婴传播的保留率从30%提高到了75%，但仍然没有达到90%的目标。2011年9月，在这项正在进行的评价中实施了B+。马拉维政府和Tingathe计划报告最近的汇总和现场数据表明，尽管B+后的吸收和保留有所改善，但水平仍然不是最理想的。在这些报告的基础上，还需要额外的患者水平数据。B+已在马拉维广泛实施；因此，使用对照(非B+点)的随机试验不能进行。然而，Kim博士的队列研究提供了一个使用患者水平数据评估B+的独特机会，而Tingathe形成了一个可以修改以改善B+的实施平台。在这份IRSDA申请中，Kim博士提出了一项三管齐下的研究，以评估和优化B+的实施。首先，在第一年和第二年，她将利用从Tingathe计划收集的纵向患者水平数据进行一项准试验性的事前/事后研究。其次，为了更好地了解B+预防母婴传播和预防母婴传播战略的实施障碍和促进者，她将对患者、卫生工作者和从事预防母婴传播服务吸收和提供的关键信息者进行半结构化的1：1访谈，进行定性研究。最后，从第三年开始，她将根据她以前的研究，利用社区参与方法以及干预地图和设计技能，设计一种改进的CHW干预措施。修改后的干预措施将在第4年和第5年使用定性和定量方法进行可接受性和可行性测试，为拟议的R01资助的随机试验做准备。金博士组建了一支出色的导师团队，帮助指导她的研究和职业发展。马拉维的主要导师Peter Kazembe博士在儿童生存、疟疾和艾滋病毒研究方面拥有30多年的经验。他将得到前IRSDA获得者、北卡罗来纳大学马拉维项目临床主任、临床和医疗专家米娜·侯赛尼普尔博士的支持。 在撒哈拉以南非洲的实施试验。美国首席导师Thomas Giordano博士是卫生服务研究方面的专家，将得到Christine Markham博士(混合方法、干预地图和评估)、温雅·陈博士(生物统计学)、Elizabeth Chiao博士(妇女健康、卫生服务研究)和Mary Paul博士(儿科艾滋病毒)的支持。共同导师伊莱恩·艾布拉姆斯博士，ICAP高级研究总监，以及防止母婴传播领域最重要的国际权威之一，完善了导师团队。在IRSDA的支持下，Kim博士寻求在以下方面获得专业知识：1)在资源有限的情况下进行实施研究；2)先进的研究设计和生物统计方法；3)定性研究；4)干预设计和评估；5)科学写作和交流技能。为了实现这一点，她将用结构化的教程和课程来补充她建议的研究，并通过BCM的临床科学家培训计划完成临床调查硕士学位。马拉维独特的研究环境、支持性的马拉维-美国导师合作和多学科课程工作将通过提供技能、经验和初步数据来为Kim博士作为实施研究员的独立做好准备，以开发一项由R01支持的随机试验，评估优化防止母婴传播实施的新战略的影响。

DESCRIPTION (provided by applicant): In 2010, there were an estimated 250,000 AIDS related child deaths, and over 330,000 children newly infected with HIV in 2011, the majority in sub-Saharan Africa. With current, efficacious, low-cost medical interventions to prevent mother-to-child transmission of HIV (PMTCT), most of these infections were preventable. The continuing high rates of AIDS related child deaths demonstrate that scientifically rigorous implementation research is needed to successfully implement evidence-based interventions, like PMTCT, in resource-limited settings. Dr. Maria Kim, Assistant Professor in the Section of Retrovirology and Global Health at Baylor College of Medicine (BCM), is focused on closing this gap between knowledge and action by learning how to identify, research, and address implementation problems and thereby improve access to and use of interventions by women and children in need. Dr. Kim's research will evaluate how to optimize the implementation of Malawi's novel national PMTCT program Option B+ (B+). Other PMTCT approaches require HIV disease staging by clinical or lab criterion to distinguish between women who need life-long treatment for their own health versus those who only require short-term medication for PMTCT. In contrast, B+ offers all HIV-infected pregnant and breastfeeding women life-long antiretroviral treatment. Therefore, B+ theoretically provides a simplified approach, which may improve uptake, retention and transmission outcomes. However, there are no published studies evaluating its efficacy. A recent commentary in the Lancet highlighted the urgent need for more data about B+, before widely implementing in other countries. As a pediatrician in Malawi, Dr. Kim participated in a study that suggested inadequate coordination of maternal and infant HIV services was significantly contributing to >70% loss-to-follow-up in PMTCT care. Based on this data, she began a prospective open cohort study to examine the impact of a strategy called Tingathe, which utilizes community health workers (CHW) to help women navigate PMTCT care. In 2011, Dr. Kim analyzed 2 years of data on >1600 women-infant pairs which demonstrated improved retention to PMTCT care from <30% to ~75%, but still did not reach the target >90%. In September 2011, B+ was implemented in the context of this ongoing evaluation. Recent aggregate and field data from Malawi government and Tingathe program reports suggest that although uptake and retention has improved post B+, levels are still suboptimal. Additional patient level data are needed to build upon these reports. B+ has already been implemented widely throughout Malawi; thus, a randomized trial utilizing a control (non B+ sites) cannot be performed. However, Dr. Kim's cohort study provides a unique opportunity to evaluate B+ using patient level data, and Tingathe forms an implementation platform that can be modified to improve B+. In this IRSDA application, Dr. Kim proposes a three-prong study to both evaluate and optimize the implementation of B+. First, in Years 1 and 2 she will conduct a quasi-experimental pre/post study utilizing the prospectively collected longitudinal patient level data from the Tingathe program. Second, to better understand both implementation barriers and facilitators to optimizing PMTCT outcomes of B+ and the Tingathe strategy she will conduct a qualitative study using semi-structured 1:1 interviews of patients, health workers, and key informants engaging in PMTCT service uptake and delivery. Finally, starting in Year 3, she will design a modified CHW intervention informed by her previous studies, utilizing a community participatory approach and intervention mapping and design skills. The modified intervention will be tested for acceptability and feasibility in Years 4 and 5 using both qualitative and quantitativ methods, in preparation for a proposed R01 funded randomized trial. Dr. Kim has assembled an outstanding mentorship team to help guide her research and career development. Dr. Peter Kazembe, the primary Malawi mentor, has over 30 years experience in child survival, malaria, and HIV research. He will be supported by Dr. Mina Hosseinipour, a former IRSDA recipient, Clinical Director of the University of North Carolina Malawi Project, and an expert in clinical and implementation trials in sub-Saharan Africa. Dr. Thomas Giordano, the primary US mentor, is an expert in health services research and will be supported by Drs. Christine Markham (mixed methods, intervention mapping and evaluation), Wenyaw Chan (biostatistics), Elizabeth Chiao (women's health, health services research), and Mary Paul (pediatric HIV). Co-mentor Dr Elaine Abrams, Senior Research Director of ICAP, and one of the foremost international authorities on PMTCT rounds out the mentorship team. With IRSDA support, Dr. Kim seeks to gain expertise in: 1) implementation research in resource- limited settings; 2) advanced study design and biostatistical methods; 3) qualitative research; 4) intervention design and evaluation; and 5) scientific writing and communication skills. To accomplish this she will complement her proposed research with structured tutorials and coursework and complete a Masters in Clinical Investigation through the Clinical Scientist Training Program at BCM. The unique Malawi research environment, supportive Malawi-US mentorship collaboration, and multi- disciplinary coursework will prepare Dr. Kim for independence as an implementation researcher by providing the skills, experience, and preliminary data to develop a R01 supported randomized trial evaluating the impact of a novel strategy to optimize the implementation of PMTCT.