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

描述（由申请人提供）：2010年，估计有250,000名与艾滋病有关的儿童死亡，2011年有超过33万名儿童新感染艾滋病毒，其中大多数在撒哈拉以南非洲。由于目前采取了有效、低成本的医疗干预措施，以防止艾滋病毒母婴传播，这些感染大多数是可以预防的。与艾滋病有关的儿童死亡率持续居高不下，这表明，在资源有限的情况下，要成功实施以证据为基础的干预措施，如预防母婴传播，需要进行科学上严格的实施研究。贝勒医学院逆转录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、研究和解决实施问题，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，从而缩小知识与行动之间的差距。Kim博士的研究将评估如何优化马拉维新的国家预防母婴传播方案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进行艾滋病毒疾病分期，以区分需要为自身健康终身治疗的妇女与只需要预防母婴传播短期药物治疗的妇女。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，B+在理论上提供了一种简化的方法，可以改善吸收、保留和传递结果。然而，尚无发表的研究评估其疗效。《柳叶刀》最近发表的一篇评论强调，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，母婴艾滋病毒服务协调不力，在预防母婴传播护理方面造成了70%的随访损失。基于这些数据，她开始了一项前瞻性开放队列研究，以检查一项名为Tingathe的战略的影响，该战略利用社区卫生工作者（CHW）帮助妇女进行预防母婴传播护理。2011年，Kim博士分析了2年的1600对母婴数据，显示预防母婴传播护理的保留率从<30%提高到~75%，但仍未达到90%的目标。2011年9月，在这一持续评估的背景下实施了B+。最近来自马拉维政府和Tingathe项目报告的汇总数据和现场数据表明，尽管B+后的吸收和保留情况有所改善，但水平仍不理想。在这些报告的基础上，需要更多的患者水平数据。B+已在马拉维全国广泛实施；因此，不能进行随机对照试验（非B+位点）。然而，Kim博士的队列研究提供了一个独特的机会来评估B+使用患者水平的数据，Tingathe形成了一个实施平台，可以修改以提高B+。在这个IRSDA申请中，Kim博士提出了一个三管齐下的研究来评估和优化B+的实施。首先，在1年级和2年级，她将利用从Tingathe项目中前瞻性收集的纵向患者水平数据进行准实验前/后研究。其次，为了更好地了解实施障碍和促进因素，以优化B+和Tingathe战略的预防母婴传播成果，她将进行一项定性研究，对参与预防母婴传播服务接受和提供的患者、卫生工作者和关键线人进行半结构化1:1访谈。最后，从3年级开始，她将根据她以前的研究，利用社区参与式方法和干预绘图和设计技能，设计一个改进的CHW干预措施。修改后的干预措施将在4年级和5年级使用定性和定量方法进行可接受性和可行性测试，为R01资助的随机试验做准备。金博士组建了一个优秀的导师团队来帮助指导她的研究和职业发展。Peter Kazembe博士是马拉维的主要导师，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Mina Hosseinipour博士的支持，她是前IRSDA接受者，北卡罗来纳大学马拉维项目的临床主任，也是临床和医学领域的专家

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.