Bierhoff Marieke, Nelson Kenrad E, Guo Nan, Jia Yuanxi, Angkurawaranon Chaisiri, Jittamala Podjanee, Carrara Verena, Watthanaworawit Wanitda, Ling Clare, Tongprasert Fuanglada, van Vugt Michele, Rijken Marcus, Nosten Francois, McGready Rose, Ehrhardt Stephan, Thio Chloe Lynne
Department of Maternal and Child health, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Amsterdam UMC, Internal Medicine, Department of Infectious Diseases, Centre of Tropical Medicine and Travel Medicine, location AMC, University of Amsterdam, Amsterdam, The Netherlands.
BMJ Open. 2020 Sep 13;10(9):e038123. doi: 10.1136/bmjopen-2020-038123.
Hepatitis B virus (HBV) remains a public health threat and the main route of transmission is from mother to child (MTCT). Tenofovir disoproxil fumarate (TDF) treatment can reduce MTCT of HBV although the optimal timing to attain undetectable HBV DNA concentrations at delivery is unknown. This protocol describes the procedures following early initiation of maternal TDF prior to 20 weeks gestation to determine efficacy, safety and feasibility of this approach in a limited-resource setting.
One hundred and seventy pregnant women from the Thailand-Myanmar border between 12 and <20 weeks gestational age will be enrolled into a one-arm, open-label, TDF treatment study with cessation of TDF 1 month after delivery. Sampling occurs monthly prenatal, at birth and at 1, 2, 4 and 6 months post partum. Measurement of tenofovir concentrations in maternal and cord plasma is anticipated in 10-15 women who have detectable HBV DNA at delivery and matched to 20-30 women with no detectable HBV DNA. Infant HBsAg status will be determined at 2 months of age and HBV DNA confirmed in HBsAg positive cases. Adverse events including risk of flare and adherence, based on pill count and questionnaire, will be monitored. Infants will receive HBV vaccinations at birth, 2, 4 and 6 months and hepatitis B immunoglobulin at birth if the mother is hepatitis B e antigen positive. Infant growth and neurodevelopment at 6 months will be compared with established local norms.
This study has ethical approval by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University (FTM ECF-019-06), Johns Hopkins University (IRB no: 00007432), Chiang Mai University (FAM-2559-04227), Oxford Tropical Research Ethics Committee (OxTREC Reference: 49-16) and by the local Tak Community Advisory Board (TCAB-02/REV/2016). The article will be published as an open-access publication.
NCT02995005, Pre-results.
乙型肝炎病毒（HBV）仍然是一种公共卫生威胁，其主要传播途径是母婴传播（MTCT）。替诺福韦酯（TDF）治疗可降低HBV的母婴传播，尽管在分娩时达到无法检测到HBV DNA浓度的最佳时机尚不清楚。本方案描述了在妊娠20周前尽早开始对母亲进行TDF治疗后的程序，以确定这种方法在资源有限的环境中的疗效、安全性和可行性。
170名妊娠12周至小于20周的泰国-缅甸边境孕妇将被纳入一项单臂、开放标签的TDF治疗研究，分娩后1个月停止使用TDF。产前每月、出生时以及产后1、2、4和6个月进行采样。预计对10-15名分娩时可检测到HBV DNA的妇女及其匹配的20-30名未检测到HBV DNA的妇女进行母体和脐带血血浆中替诺福韦浓度的测量。婴儿在2个月大时确定HBsAg状态，HBsAg阳性病例中确认HBV DNA。基于药丸计数和问卷监测不良事件，包括爆发风险和依从性。如果母亲是乙肝e抗原阳性，婴儿将在出生时、2、4和6个月接种乙肝疫苗，并在出生时接种乙肝免疫球蛋白。将6个月时婴儿的生长和神经发育与既定的当地标准进行比较。
本研究已获得玛希隆大学热带医学院伦理委员会（FTM ECF-019-06）、约翰霍普金斯大学（IRB编号：00007432）、清迈大学（FAM-2559-04227）、牛津热带研究伦理委员会（OxTREC参考编号：49-16）以及当地夜丰颂社区咨询委员会（TCAB-02/REV/2016）的伦理批准。文章将作为开放获取出版物发表。
NCT02995005，预结果。
