Pregnant women with high hepatitis B virus (HBV) DNA load still transmit to their infants despite infant HB immunoglobulin (HBIg) and HB vaccine.
This phase III, double-blind, clinical trial randomized pregnant women with HBV infection (HBsAg and HBeAg positive) to tenofovir DF (TDF) 300 mg once daily or matching placebo (1:1) from 28 weeks gestation through 2 months postpartum in 17 sites in Thailand. All infants received HBIg at birth, and vaccine at birth, 1, 2, 4 and 6 months of age. Main inclusion criteria were: age ≥18 years, confirmed ALT ≤60 IU/L, negative HIV and hepatitis C serology, creatinine clearance >50 mL/min, and no history of TDF treatment. Mothers and infants were followed until 12 months postpartum. The primary efficacy endpoint was detection of HBsAg confirmed by HBV DNA at 6 months of age. The target sample size was 156 evaluable mother/infant pairs per arm to detect a difference in HBV infected infants of 3% (TDF) vs. 12% (placebo) with 90% power accounting for one interim efficacy analysis, using a one-sided Fisher’s exact test. Analyses are based on data through 6 months postpartum.
From January 2013 to August 2015, 331 women (168 TDF, 163 placebo) were enrolled. Median age at enrollment was 26 years, gestational age (GA) 28.3 weeks, weight 61 kg, and HBV DNA load 8.0 log10 IU/mL. The 322 (97%) on-study deliveries (85 Cesarean, 26%) resulted in 323 live births (including 2 twin pairs) and 1 stillbirth (TDF arm). Median GA at delivery was 38.9 weeks. Median birth weight was 3,050 g (3,028 g TDF, 3,061 g placebo). There were 21 (7%) preterm newborns (8 TDF, 13 placebo). 322 (>99%) infants received HBV vaccine a median of 1.2 hrs. after birth and 320 (99%) HBIg a median of 1.3 hrs. after birth. In the primary complete case analysis at 6 months (table), 0/147 infants had HBV infection in the TDF arm vs. 3/147 (2.0%) in the placebo arm (p=0.12). One newborn with gross abnormalities (placebo arm) died soon after birth. Following study treatment discontinuation, 9 (6%) women experienced an ALT >300 IU/mL in the TDF arm vs. 5 (3%) in the placebo arm (two-sided p=0.29). The proportions of maternal and infant adverse events, and infant growth were similar between arms.
TDF resulted in a small non-significant reduction in perinatal HBV transmission beyond the low risk achieved with the recommended use of HBIg and HBV vaccine. It appeared safe for pregnant women and their infants and there was no evidence of impaired infant growth.