Expected Eight-Week Prenatal Versus Twelve-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-To-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-label, Randomized Controlled Trial

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3–9.0 log 10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected 8 week) or to 4 weeks postpartum (expected 12 week) were randomly enrolled at a 1:1 ratio and followed until 6 months postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary end point was the safety of mothers and infants. The secondary end point was the HBV-MTCT rate of infants at the age of 7 months. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in 2 groups completed the study. Overall, TAF was well tolerated, no one discontinued the therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%–1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%–1.6%). The infants' physical development at birth (n = 231) and at 7 months (n = 222) was normal. Furthermore, 97.0% (224/231, 95% CI 93.9%–98.5%) of women achieved HBV DNA <5.3 log 10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%–11.1%) and 0% (0/222, 95% CI 0%–1.7%) at the age of 7 months. Comparatively, 15.1% (18/119, 95% CI 9.8%–22.7%) vs 18.3% (22/120, 95% CI 12.4%–26.2%) of women in the 2 groups had mildly elevated alanine aminotransferase levels at 3 months and 6 months postpartum, respectively ( P = 0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%–3.1%] vs 0% [0/120, 0%–3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected 8-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.