Antiviral TDF Unhelpful in Decreasing Mother-to-Child HBV

Gonzague Jourdain, MD, PhD

Giving women an antiviral drug commonly prescribed to treat the hepatitis B virus did not significantly reduce mother-to-child transmission when administered in conjunction with the standard HBV regimen for infants, a new study shows.

The drug, tenofovir disoproxil fumarate (TDF) was taken during pregnancy and after delivery by HBV-positive women in a phase 3 clinical trial in Thailand. The babies received the recommended combination of HBV vaccine and hepatitis B immune globulin (HBIG).

“Our study suggests that adding TDF to the current regimen seems to have little effect on infant infection rates when transmission rates are already low," said team member Nahida Chakhtoura, MD, a medical officer at the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study was funded by the NIH and published in the New England Journal of Medicine.

The World Health Organization (WHO) recommends that all newborns receive their first dose of hepatitis B vaccine within 24 hours of delivery. Infants born to HBV-infected mothers are also prescribed HBIG.

Even when this protocol is followed, mother-to-child transmission can occur when women have high levels or mutated versions of the virus, the researchers wrote.

“Most of the 4.5 million new HBV infections are due to mother-to-child transmission worldwide,” study lead author Gonzague Jourdain, MD, PhD, told MD Magazine. “The elimination of mother-to-child transmission will require strategies that are not limited to the use of vaccine and immune globulin in newborns.’’

Minimal evidence exists to support the effectiveness of using antiviral drugs to prevent mother-to-child HBV transmission, researchers noted. This has led to conflicting global recommendations.

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have not registered TDF for anti-HBV use. The WHO also has not recommended this course, said Jourdain, who is affiliated with Thailand’s Chiang Mai University, Harvard University’s TH Chan School of Public Health, and France’s Institut de Recherche pour le Développement (IRD).

“However, the 3 major associations of experts for the study of liver diseases (AASLD, EASL, and APSL) have suggested using this approach, although no clear protocol has been proposed so far,” Jourdain said.

Some antivirals have been studied in conjunction with mother-to-child HBV transmission.

“Lamivudine has not been shown effective in this setting and there are concerns that its use may lead to HBV resistance to this drug and other antivirals of the same class,’’ Jourdain said. "Telbivudine, a potent anti-HBV agent, had been shown efficient in an open comparative study in China, but this drug is no longer manufactured due to safety issues.’’

In a previous clinical trial in China, women who received TDF showed a significantly lower rate of mother-to-child HBV than those who got standard care, the researchers wrote. However, there were several differences between this study and the 1 conducted in Thailand.

“Our design differed from the design of that trial, which was not placebo-controlled and not double-blind,” the authors wrote, adding that there were other differences as well.

Gilead Sciences, the maker of TDF, funded the China trial.

To assess whether maternal use of TDF might reduce or prevent HBV transmission to their babies, Jourdain and his team screened more than 2,500 women at 17 hospitals associated with Thailand’s Ministry of Public Health. The researchers selected 331 pregnant women who had HBV and divided them into two groups. One group of 163 received a placebo. The second group of 168 received TDF in intervals starting at 28 weeks of pregnancy and ending two months after delivery.

A total of 294 infants, 147 in each group, were followed through age 6 months. None of the babies of mothers given TDF had HBV at that age. Three infants in the placebo group contracted the virus. “This was lower than expected, and this difference was not significant,” Jourdain said.

The study had enough participants to detect statistical differences if the transmission rate in the placebo group reached at least 12%, researchers noted. The low transmission rate might relate to the higher number of HBV vaccine doses given in Thailand, lower rates of amniocentesis and Cesarean section deliveries in the study, or the lower prevalence of mutated viruses in Thailand.

As for further research, Jourdain said that in many low and middle-income countries, use of immune globulin is limited due to logistics and costs.

“Whether the use of antivirals in infected mothers could lower the risk of perinatal transmission in these settings where immune globulin is not systematically administered to infants born to infected mothers remains an important research question,’’ he said.

The study, “Prevention of mother-to-child transmission of hepatitis B virus,” was published online in BMC Infectious Diseases.