Maternal TDF Therapy, Infant Vaccination Prevents Mother-to-Child HBV Transmission

Calvin Pan, MD

Credit: AASLD

Tenofovir disoproxil fumarate (TDF) at gestational week 16 combined with hepatitis B virus (HBV) vaccinations for infants effectively prevents mother-to-child HBV transmission, according to findings from a recent study.¹

Results show initiating maternal TDF therapy at week 16 combined with HBV vaccinations for infants is non-inferior to standard care of TDF at gestational week 28 combined with HBV vaccinations and HBV immune globulin (HBIG) for infants in pregnant women with HBV and high levels of viremia. This suggests this approach could be a viable option for preventing mother-to-child HBV transmission in geographic areas where HBIG is not available.¹

The World Health Organization estimates 254 million people were living with chronic hepatitis B infection in 2022, with 1.2 million new infections each year. In highly endemic areas, hepatitis B is most commonly spread from mother to child at birth, underscoring the importance of preventing this type of transmission to aid viral hepatitis elimination efforts and reduce complications like cirrhosis and hepatocellular carcinoma.²

“Current management strategies involve testing pregnant individuals for hepatitis B surface antigen (HBsAg) and providing HBV vaccination with HBV immune globulin (HBIG) to their infants,” Calvin Pan, MD, a distinguished professor of medicine at NYU School of Medicine, and colleagues wrote.¹ “However, HBIG is unavailable in most countries, particularly in resource-limited regions, because of the poor availability of refrigeration and high costs. The limited availability of HBIG presents a challenge to HBV elimination in these countries.”

To determine whether initiating TDF at gestational week 16 combined with HBV vaccinations for infants is non-inferior to the standard care of TDF at gestational week 28 combined with HBV vaccinations and HBIG for infants in preventing mother-to-child transmission, investigators conducted an unblinded, 2-group, randomized, noninferiority clinical trial in 7 tertiary care hospitals in China.¹

A total of 280 pregnant individuals 20-35 years of age with chronic hepatitis B and HBV DNA levels > 200,000 IU/mL were enrolled between June 4, 2018, and February 8, 2021. Participants were randomly assigned in a 1:1 ratio to receive either 300 mg of TDF starting at gestational week 16 with HBV vaccinations for the infant or 300 mg of TDF starting at gestational week 28 with HBV vaccinations and HBIG administered to the infant. This process was stratified by hospitals and maternal HBV DNA levels.¹

All infants received 10 μg of the HBV vaccine within 12 hours of birth, with additional doses administered at 1 and 6 months. Infants in the standard care group also received 100 IU of HBIG at birth. Infants in the experimental group received HBIG if their mother’s HBV DNA levels exceeded 200 000 IU/mL either at delivery or at the last available measurement before delivery.¹

The primary outcome was the mother-to-child transmission rate, defined as detectable HBV DNA > 20 IU/mL or hepatitis B surface antigen positivity in infants at age 28 weeks. Noninferiority was established if the transmission rate in the experimental group did not increase by more than an absolute difference of 3% compared with the standard care group, as measured by the upper limit of the 2-sided 90% CI.¹

Among the cohort (n = 280), 265 (95%) participants completed the study. In total, 273 live births were delivered by 269 mothers (n = 131 experimental; n = 142 standard care). At age 28 weeks, 269 (98.5%) infants were available for outcome assessment, including 128 (97.7%) in the experimental group and 141 (99%) in the standard care group.¹

Among all live-born infants, including 8 infants not analyzed in the per-protocol analysis, all had undetectable levels of HBV DNA at birth. However, 1 infant in the experimental group with protocol nonadherence tested positive for HBsAg at birth and was classified as a case of HBV infection.¹

The mother-to-child transmission rate was 0.76% (1/131) in the experimental group and 0% (0/142) in the standard care group. The between-group difference was 0.76% with an upper limit of the 2-sided 90% CI of 1.74%, which falls within the 3% noninferiority margin. In the per-protocol analysis, the mother-to-child transmission rate was 0% in both groups, with an upper limit of the 2-sided 90% CI of 1.43% that again met the criteria for noninferiority.¹

Investigators noted a statistically significantly greater percentage of mothers in the experimental group achieved HBV DNA levels < 200,000 IU/mL (99.2% vs 94.2%; 2-sided 95% CI, 0.1% to 10.0%; P = .02) compared with the standard care group.¹

Maternal TDF therapy was generally well-tolerated, with only 1 mother (0.36%) discontinuing TDF due to nausea. The 3 most common adverse events in the entire cohort were maternal ALT elevation (25%), upper respiratory infection (14.6%), and vomiting (12.9%). Among live-born infants, the rates of grade III or IV adverse events were similar between groups.¹

In the experimental group, there was 1 pregnancy termination and 4 fetal losses, including 1 miscarriage and 3 stillbirths. However, investigators determined these outcomes were unrelated to TDF therapy, except for 1 case, which was deemed inconclusive.¹

Investigators acknowledged multiple limitations to these findings, including the short follow-up period; the potential lack of generalizability to populations outside of China; the unblinded nature of the clinical trial; and the fact that some participants in the intervention group received HBIG, which may have biased the study toward a finding of noninferiority.¹

“Among pregnant women with HBV and high levels of viremia, initiating TDF at gestational week 16 combined with HBV vaccination for infants was non-inferior to the standard care of TDF at gestational week 28 with both HBV vaccination and HBIG for infants. These results support starting TDF at gestational week 16 combined with infant HBV vaccination to prevent MTCT HBV transmission in regions where HBIG is not available,” investigators concluded.¹

References

1. ^{Pan CQ, Dai E, Mo Z, et al. Tenofovir and Hepatitis B Virus Transmission During Pregnancy A Randomized Clinical Trial. JAMA. doi:10.1001/jama.2024.22952}
2. ^{World Health Organization. Hepatitis B. Newsroom. April 9, 2024. Accessed November 14, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b}