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

2010年，估计有250,000名儿童死于艾滋病，超过330,000名儿童 2011年新感染艾滋病毒，大部分在撒哈拉以南非洲。最新的、有效的、低成本的 预防母婴传播艾滋病毒的医疗干预(母婴传播)，其中大多数感染 是可以预防的。与艾滋病有关的儿童死亡率持续居高不下表明，从科学上讲 需要进行严格的实施研究，才能成功实施循证干预措施，如 防止母婴传播，在资源有限的情况下。反转录病毒学和病毒科助理教授Maria Kim博士 贝勒医学院(BCM)的全球健康，专注于缩小知识和知识之间的差距 行动，通过学习如何识别、研究和解决实施问题，从而改进 有需要的妇女和儿童获得和利用干预措施。 金博士的研究将评估如何优化马拉维新国家计划的实施 防止母婴传播方案选项B+(B+)。其他预防母婴传播方法需要由临床或实验室对HIV疾病进行分期 区分那些为了自己的健康而需要终身治疗的女性和那些 只需要对母婴传播进行短期药物治疗。相比之下，B+为所有感染艾滋病毒的孕妇和 哺乳妇女终身抗逆转录病毒治疗。因此，B+理论上提供了一种简化的 方法，这可能会改善吸收、保留和传播结果。然而，没有 已发表的评估其疗效的研究。《柳叶刀》最近的一篇评论强调了 更多关于B+的数据，然后在其他国家广泛实施。 作为马拉维的一名儿科医生，金博士参与了一项研究，该研究表明 母婴艾滋病毒服务对预防母婴传播护理中70%的随访损失起到了重要作用。 基于这些数据，她开始了一项前瞻性的开放队列研究，以检查一项名为 Tingathe利用社区卫生工作者(CHW)帮助妇女适应预防母婴传播的护理。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，这些配对的保留率提高了 预防母婴传播治疗从30%降至~75%，但仍未达到90%的目标。 2011年9月，在这项正在进行的评价中实施了B+。最近的合计 马拉维政府和Tingathe计划报告的现场数据表明，尽管吸纳量和 保留率在B+后有所改善，但水平仍处于次优水平。需要额外的患者级别数据来构建 根据这些报告。B+已在马拉维各地广泛实施；因此，这是一项随机试验 不能使用控制(非B+站点)。然而，金博士的队列研究提供了一个独特的 使用患者级别数据评估B+的机会，Tingathe形成了一个实施平台，可以 被修改以提高B+。 在此IRSDA应用程序中，Kim博士提出了一项三管齐下的研究，以评估和优化 B+的实现。首先，在第一年和第二年，她将进行一项准实验性的前后研究，利用 前瞻性收集了Tingathe计划的纵向患者水平数据。第二，做得更好 了解B+预防母婴传播成果的实施障碍和促进者 Tingathe策略她将使用对患者的半结构化1：1采访进行定性研究， 卫生工作者和从事预防母婴传播服务吸收和提供的主要信息者。最后，从 第三年，她将根据她以前的研究设计一种改良的CHW干预措施，利用 社区参与式方法和干预、地图绘制和设计技能。修改后的干预措施 将在第四年和第五年使用定性和定量两种方法测试可接受性和可行性 方法：为拟议的R01资助的随机试验做准备。 金博士组建了一支优秀的导师团队，帮助指导她的研究和职业生涯 发展。马拉维的主要导师Peter Kazembe博士在儿童方面有30多年的经验 生存、疟疾和艾滋病毒研究。他将得到前IRSDA成员米娜·侯赛尼普尔博士的支持 获奖者，北卡罗来纳大学马拉维项目临床主任，临床和 在撒哈拉以南非洲的实施试验。托马斯·佐丹诺博士，美国的主要导师，是一位 卫生服务研究，并将得到Christine Markham博士的支持(混合方法，干预 测绘和评价)、温雅·陈(生物统计)、伊丽莎白·乔(妇女保健、保健服务 研究)和玛丽·保罗(儿科艾滋病毒)。共同导师ICAP高级研究总监Elaine Abrams博士， 防止母婴传播方面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)资源- 受限环境；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)科学写作和沟通技巧。要做到这一点 她将用结构化的教程和课程作业来补充她提议的研究，并完成 通过BCM临床科学家培训计划获得临床研究硕士学位。 独特的马拉维研究环境，支持性的马拉维-美国导师合作，以及多个 学科课程将为金博士独立成为一名实施研究员做好准备 提供技能、经验和初步数据以开发R01支持的随机试验 评估一项新战略的影响，以优化防止母婴传播的执行。

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 quantitative 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.