Tenofovir, Vaccine Combo Eliminates Mom-to-Child HBV Transmission

Earlier maternal tenofovir disoproxil fumarate (TDF) combined with infant vaccination completely eliminated vertical transmission of chronic hepatitis B virus (HBV) from highly viremic mothers, even without the use of hepatitis B immunoglobulin (HBIg), a randomized trial conducted in China found.

At 28 weeks postpartum, mother-to-child transmission was an identical 0% with early maternal TDF therapy starting at 14-16 weeks gestational age (followed by infant HBV vaccination) versus maternal TDF therapy starting at 28 weeks gestational age (followed by infant vaccination plus HBIg), reported Calvin Pan, MD, of the NYU Langone Health in New York City.

At delivery, mothers in the early TDF group had significantly lower HBV-DNA levels (2.37 vs 3.62 log₁₀ IU/mL, P<0.001), and a higher proportion had HBV-DNA levels below 200,000 IU/mL (99% vs 94%, P=0.04).

There was no significant difference seen in the rates of congenital defects among infants, at 3.1% in the early group and 6.4% in the late group (P=0.22), according to findings presented at the annual Liver Meeting sponsored by the American Association for the Study of Liver Diseases.

In combination with infant vaccination, Pan said the findings in the investigational arm showed that initiating TDF at week 16 of gestational age "could effectively prevent transmission, which is comparable to the current standard of care, with no safety signals."

William Carey, MD, of the Cleveland Clinic in Ohio, told MedPage Today that the current study took advantage of the fact that HBIg is in limited supply to design a new and simpler strategy -- omitting HBIg altogether.

"Anything that can be done to simplify the process of protecting [a] baby would be welcome," said Carey, who was not involved in the study.

Reached for comment, Andrew Talal, MD, MPH, of the University at Buffalo in New York, told MedPage Today that further studies "should investigate this approach to determine the generalizability of these findings to other populations."

"It is important to recognize that this is a very small sample size, inadequate to determine potential harms that occur infrequently," Carey explained. "If confirmed, it is likely that the two-step strategy will become common practice."

Chronic HBV is a global public health threat that affects nearly 296 million individuals. For mothers who have HBV DNA levels greater than 200,000 IU/mL, the World Health Organization (WHO) recommends maternal use of TDF combined with infant HBV vaccination and HBIg.

Given the scarcity of HBIg in many developing countries, the researchers evaluated if earlier maternal TDF and infant vaccination, but without HBIg, could similarly protect against mother-to-child HBV transmission. A prior study in Cambodia testing a similar strategy also showed a 0% vertical transmission rate.

From June 2018 to February 2021, researchers enrolled 265 mothers with chronic HBV (and HBV DNA levels above 200,000 IU/mL) who gave birth to 269 infants. TDF was given at a dose of 300 mg daily. All infants were given active immunoprophylaxis.

Mother-to-child transmission was defined by being positive for HBV surface antigen (HBsAg) or having HBV-DNA levels above 20 IU/mL. Primary outcome results were the same in both modified intention-to-treat and per-protocol analyses, and a sensitivity analysis showed a 2% mother-to-child transmission rate among the early TDF group, indicating a comparable effectiveness to the current standard of care.

Mothers in the study had a mean age of approximately 28, and their average body mass index was 22.

TDF therapy was well tolerated, said Pan, while no patients discontinued because of severe adverse events (AEs). Both groups showed comparable frequency and severity of safety parameters, such as severe AEs, glomerular filtration rates during treatment, and postpartum alanine aminotransferase (ALT) flares, he explained.

Study limitations included a short follow-up and lack of placebo. Four infants in the early group received HBIg, said Pan.

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