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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 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. 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 two groups completed the study. Overall, TAF was well tolerated, no one discontinued 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 seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 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 seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.
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BACKGROUND & AIMS: Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. METHODS: Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. RESULTS: One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. CONCLUSIONS: TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.