Prevention of mother-to-child transmission of hepatitis B virus: protocol for a one-arm, open-label intervention study to estimate the optimal timing of tenofovir in pregnancy
François Nosten,
Rose McGready,
Verena Carrara,
Stephan Ehrhardt,
Chaisiri Angkurawaranon,
Nan Guo,
Yuanxi Jia,
Marieke Bierhoff,
Kenrad E Nelson,
Podjanee Jittamala,
Wanitda Watthanaworawit,
Clare Ling,
Fuanglada Tongprasert,
Michele van Vugt,
Marcus Rijken,
Chloe Lynne Thio
Affiliations
François Nosten
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Rose McGready
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, Thailand
Verena Carrara
1Infectious Diseases Data Observatory (IDDO), University of Oxford, UK
Stephan Ehrhardt
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Chaisiri Angkurawaranon
Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Nan Guo
Department of Cardiology, Hebei Medical University, Cangzhou Central Hospital, Cangzhou, Hebei, China
Yuanxi Jia
Department of Medicine, School of Medicine, Johns Hopkins University, 1830 East Monument Street, Suite 8068, Baltimore, MD 21287, USA
Marieke Bierhoff
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
Kenrad E Nelson
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA
Podjanee Jittamala
Department of Maternal and Child health, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Wanitda Watthanaworawit
Department of Microbiology, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
Clare Ling
Centre for Tropical Medicine and Global Health, Oxford University, Oxford, Oxfordshire, UK
Fuanglada Tongprasert
Department of Obstetrics and Gynecology, Chiang Mai University, Suthep, Chiang Mai, Thailand
Michele van Vugt
Internal Medicine, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
Marcus Rijken
Department of Obstetrics and Gynecology, Utrecht University, Utrecht, The Netherlands
Chloe Lynne Thio
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Introduction 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.Methods and analyses 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.Ethics and dissemination 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.Trial registration number NCT02995005, Pre-results.
