Prenatal tenofovir didn’t reduce the rate of hepatitis B among infants born to women infected with the virus.

Among 322 6-month-olds, the rate of HBV transmission was 0 in those whose mothers received the antiviral during pregnancy and 2% among those whose mothers received placebo – not a statistically significant difference, Gonzague Jourdain, MD , and his colleagues reported in the New England Journal of Medicine .

All of the infants in the study, who were born in Thailand, got hepatitis B immune globulin and began a 5-dose HBV vaccination schedule within the first few hours after birth, something that “may have contributed to the low rate of HBV transmission that was observed” in the study, said Dr. Jourdain, a visiting scientist at the Harvard School of Public Health, Boston.

The study randomized 331 pregnant women with proven HBV infections to either tenofovir or placebo from 28 weeks’ gestation to 2 months post partum. All infants received HBV immune globulin at birth, and HBV vaccine at birth and at 1, 2, 4, and 6 months. The primary endpoint was confirmed HBV infection in the infant at 6 months.

Women were a mean of 28 weeks pregnant at baseline, with a mean viral load of 8.0 log10 IU/mL. Most women (about 90% of each group) had an HBV DNA of more than 200,000 IU/mL – a level associated with an increased risk of perinatal HBV infection despite vaccination.

There were 322 deliveries, resulting in 319 singletons, two pairs of twins, and one stillbirth. Postpartum infant treatment was quick, with a median of 1.3 hours from birth to administration of immune globulin and a median of 1.2 hours to administration of the first dose of the vaccine.

At 6 months, there were no HBV infections in the tenofovir-exposed group and 3 (2%) in the placebo group – a nonsignificant difference (P = .12).

Tenofovir was safe for both mother and fetus, with no significant adverse events in either group. The incidence of elevated maternal alanine aminotransferase level (more than 300 IU/L) was 6% in the tenofovir group and 3% in the placebo group, also a nonsignificant finding.

Dr. Jourdain and his colleagues noted that the 2% transmission rate in the placebo group is considerably lower than the 7% seen in similar studies and could be related to the rapid postpartum administration of HBV immune globulin and vaccine. If this is the case, prenatal antivirals could be more effective in countries where postpartum treatment is delayed or inconsistent.

“Maternal use of tenofovir may prevent transmissions that would occur when the birth dose is delayed, but its exact timing has not been reported consistently in previous perinatal studies,” the team said.

Another question is whether the stringent, 5-dose infant HBV vaccine series required in Thailand is simply more effective than schedules that have fewer doses or are combined with other vaccines and delivered later.

“It remains unclear whether the administration of more vaccine doses is more efficacious than the administration of the three vaccine doses that is recommended in the United States and by the World Health Organization.”

Dr. Jourdain had no financial disclosures relevant to the study, which was sponsored by the National Institute of Child Health and Human Development.

SOURCE: Jourdain G et al. N Engl J Med. 2018;378:911-23 .


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