Maternal TDF, infant HBV vax, HBIg-free strategy prevent infant hep B

In the absence of infant hepatitis B immune globulin (HBIg), maternal tenofovir disoproxil fumarate (TDF) prophylaxis combined with infant hepatitis B virus (HBV) immunization provide sufficient protection against HBV infection in infants, findings from the iTAP-2 study suggest. However, the risk of infection was not demonstrably below 2 percent.

Of the 423 pregnancies in the primary analysis, four singleton infants had HBV infection at 6 months, yielding an infection risk of 0.95 percent (90 percent confidence interval [CI], 0.32–2.15), with the upper CI limit above the 2 percent hypothesized.

“All sensitivity analyses confirmed the results. There was only one infected infant who had HBV DNA detectable in peripheral blood at birth at a very low level, which shows that none of them were infected in utero. There were no phylogenetic differences between maternal and infant viruses,” said Dr Gonzague Jourdain from Chiang Mai University in Thailand, at CROI 2025.

In terms of infant safety, there were no concerns, he added. None of the six infant deaths were deemed related to TDF exposure. [CROI 2025, abstract 117]

HBIg protection critical but availability is limited

“If a pregnant woman has a high HBV load or a positive Hb e-antigen (HBeAg+) test, the combination of maternal TDF prophylaxis, active immunization, and infant HBIg is recommended to prevent transmission. This combination ensures long-term immune protection,” said Jourdain.

“HBIg provides an early temporary intervention barrier that prevents the establishment of a liver infection. This protection is especially critical if the infant is exposed to breakthrough viruses, at the very time when the protection provided by [TDF] is defaulting,” he explained.

However, HBIg is inconsistently available – it is not available at all in many countries like Laos, where HBIg has never been registered, he continued. “We hypothesized that HBIg could be omitted if mums receive TDF prophylaxis.”

The team conducted a prospective, single-arm trial on 503 mums (median age 26.3 years) from Thailand and Laos. HBeAg+ mums without HIV infection and with no contraindication to TDF received TDF prophylaxis from week 28 of pregnancy to 2 months postpartum. HB vaccines were administered to newborns as soon as possible after birth (median 60 min) and then according to national schedules (4–6 weeks, 8–10 weeks, 14–16 weeks, and 6 months).

At baseline, 97.6 percent of mums had HBV DNA >5.3 log₁₀ IU/mL (=200,000) and median HBV DNA load was 8 log₁₀ IU/mL. At delivery, 92.4 percent had HBV DNA ≤5.3 log₁₀ IU/mL and the median HBV DNA dropped to 3.8 log₁₀ IU/mL.

A total of 501 infants were born including three sets of twins. At 6 months, 474 infants had HB surface antigen test results.

The proportion of women with HBV DNA load ≤200,000 IU/mL gradually increased from enrolment (2.4 percent) to gestational age (GA; 66.6 percent [GA32] and 82.2 percent [GA36]) and delivery (92.4 percent).

Alanine aminotransferase values were above normal in most mums (52 grade 3, 16 grade 4) but none were symptomatic, and no maternal deaths were reported.

Guideline adjustments

“There was no evidence that any infant already had an established liver infection before birth, suggesting the high efficacy of maternal prophylaxis, even in cases of inconsistent adherence,” said Jourdain.

“From a public health perspective, TDF prophylaxis did prevent in utero infection before vaccine administration, but without HBIg, we did observe a transmission rate that would be unacceptable for HIV,” he stressed. “The 2024 WHO guidelines for PMTCT*, which exclude HBIg, might require adjustments at least for women from Southeast Asia and the Pacific because they have highly replicative viruses.”

The findings align with the results of two smaller studies evaluating maternal TDF prophylaxis with the HBIg-free strategy, wherein transmissions were reported in only a small fraction of infants. [Lancet Infect Dis 2022;22:1181-1190; JAMA 2025;333:390-399]