Vertical Transmission in Mothers Taking TAF With Exceptionally High Viral Load

ABSTRACT Published studies on tenofovir alafenamide (TAF) therapy for preventing vertical transmission of hepatitis B virus (HBV) have primarily enrolled mothers with viremic levels of approximately 7 log 10 IU/mL. This study aimed to evaluate the efficacy and safety of TAF therapy in preventing mother‐to‐child transmission (MTCT) in mothers with exceptionally high viral loads, defined as HBV DNA levels > 2,000,000 IU/mL. Hepatitis B e antigen (HBeAg)‐positive mothers with HBV DNA levels > 2,000,000 IU/mL were prospectively enrolled from four hospitals and initiated on TAF therapy between gestational weeks 26 and 28, continuing until delivery. All infants received immunoprophylaxis and were followed up to 28 weeks postpartum. The primary endpoints were the MTCT rate and the occurrence of congenital abnormalities in infants. Secondary outcomes included maternal HBV suppression at delivery and the safety of both mothers and infants. Among 137 mothers screened, 120 were enrolled in TAF therapy, and 121 infants completed the study. At delivery, 93.3% (112/120) of mothers achieved HBV DNA levels < 200,000 IU/mL. At birth, 0.8% (1/121) of infants had a congenital malformation, and 9.9% (12/121) tested positive for HBsAg. The vertical transmission rate was 2% (2/121, intention‐to‐treat) at 28 weeks of age. No severe adverse effects were reported in mothers or infants. On‐treatment and postpartum alanine aminotransferase (ALT) flares after TAF cessation occurred in 7.5% (9/120) and 41.1% (46/112) of mothers, respectively, alongside viral rebound after cessation. Infant physical development remained within normal ranges based on national reference standards. In summary, approximately 2% of mothers on TAF therapy during late pregnancy experienced MTCT, despite proper immunoprophylaxis for their infants. Extending the treatment duration beyond 12 weeks for mothers with extremely high viral loads is recommended to improve MTCT prevention. No safety concerns were observed for either mothers or infants. Trial Registration: ClinicalTrials.gov identifier: NCT04237376