Background
Hepatitis B (HB) vaccination starting with a birth dose and HB immune globulin (HBIg) are given to prevent HB in infants, but HBIg is not available in many settings. This trial aimed to assess whether the risk of infection is below 2% in infants born to HBeAg positive mothers prescribed tenofovir disoproxil fumarate (TDF) prophylaxis, with the infants receiving HB vaccination according to national guidelines without HBIg. This is the regimen recommended by the 2024 WHO Guidelines.
Methods
This prospective, single arm clinical trial was designed to enroll 499 pregnant women with positive HBsAg and HBeAg tests at 28 weeks gestational age (GA), no contraindications to TDF, and no HIV infection in 8 public hospitals in Laos and 12 in Thailand (NICHD R01 HD092527) . An HBV DNA load measurement was scheduled during pregnancy to assess adherence and consider infant HBIg if needed. The primary outcome was infant HBV infection (positive HBsAg test confirmed by HBV DNA PCR at 6 months of age). The primary analysis was performed in infants who had an HBsAg test at 6 months of age, who did not receive HBIg, and whose mothers had no evidence of an unsatisfactory virologic response after initiating TDF, defined as HBV DNA load measurement between 20 days after starting TDF and 36 weeks GA that had not decreased by >10-fold in IU/mL from baseline and was >200,000 IU/mL. The proportion of pregnancies with HBV infection at 6 months was estimated along with a two-sided 90% Clopper-Pearson confidence interval (CI).
Results
Baseline and follow up data are summarized in the Table. No safety concerns were identified. There were 6 infant deaths, none deemed related to TDF exposure. In the primary analysis, 4 singleton infants of 423 pregnancies were infected at 6 months, yielding an infection risk of 0.95% (90% CI: 0.32%-2.15%), with the upper limit above the 2% hypothesized. In addition, one infant had a first HBsAg positive test (confirmed by HBV DNA PCR) at 4 months but was then lost to follow up, and another was infected but with an unsatisfactory maternal response: both cases were part of those excluded from the primary analysis. Sensitivity analyses confirmed the findings.
Conclusions
Maternal TDF prophylaxis and active immunization was efficacious in preventing HBV infection but the risk of infection was not demonstrably below 2%. These findings highlight the level of efficacy achievable when adhering to the 2024 WHO guidelines in South East Asia.
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