Mothers who took tenofovir disoproxil fumarate (Viread) during pregnancy did not have a significantly lower risk of transmitting hepatitis B virus (HBV) to their infants compared with those who used standard preventive therapy, according to research presented at the 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018) last week in Boston.
Rates of HBV transmission were very low overall, with no infants in the tenofovir group and three in the standard prophylaxis groups having confirmed HBV infection at 6 months of age, reported Gonzague Jourdain of the Institut de Recherche Pour le Développement in Chiang Mai, Thailand.
HBV is a blood-borne virus that can be transmitted from mother to infant during gestation or delivery. Standard measures to prevent mother-to-child transmission involve giving the baby injected HBV antibodies (hepatitis B immune globulin, or HBIG) and the first dose of the HBV vaccine.
The iTAP study was a randomised clinical trial to evaluate whether tenofovir – the standard of care for treating chronic hepatitis B – could further reduce the risk of perinatal transmission when added to the usual preventive measures. Antiviral treatment could potentially lower the risk both by reducing the mother's HBV viral load and acting as pre-exposure prophylaxis for the infant.
The study included 331 pregnant women (median age 26 years) at 17 hospitals in Thailand who had active chronic HBV infection, indicated by hepatitis B surface antigen (HBsAg) and hepatitis 'e' antigen (HBeAg) positivity. They had normal kidney function at baseline, a concern because tenofovir DF can cause kidney problems in susceptible individuals. Women with HIV or hepatitis C co-infection were excluded.
The women were randomly assigned to receive 300mg tenofovir DF or placebo once daily starting at 28 weeks of gestation and continuing through 2 months postpartum. Infants received HBIG at birth and HBV vaccine doses at birth and at 1, 2, 4 and 6 months of age. (The infant vaccine schedule used in the UK and in the US and recommended by the World Health Organization involves only three doses.) Breastfeeding was encouraged.
There were 323 live births and 286 infants remained in follow-up for 12 months. About a quarter of births were by Caesarean section, which raises the risk of HBV transmission.
As reported at last year's CROI and published recently in The New England Journal of Medicine, there were no HBV infections in the tenofovir group and three infections (2%) in the placebo group by 6 months of age, according to HBV DNA PCR testing.
At this year's CROI the researchers reported that no additional infections were observed in either group between 6 and 12 months of age. Among 275 infants tested for HBV antibodies at 12 months, four of them – all in the placebo group, including the three infected babies – had levels below 10 IU/l, indicating that vaccination was ineffective.
Treatment with tenofovir DF was generally safe and well tolerated. Women in the tenofovir and placebo groups had similar rates of serious or grade 3/4 adverse events. Nine women (6%) in the tenofovir group and six (4%) in the placebo group experienced ALT flares (> 300 IU/l) after stopping therapy, a known effect of antiviral discontinuation.
The proportion of infants with serious or grade 3/4 adverse events was also similar in both the tenofovir and placebo groups, and growth parameters including weight, height and head circumference were comparable at 12 months.
An iTAP sub-study looked at changes in bone mineral density among the women and infants. Tenofovir DF has been shown to cause a small amount of bone loss when taking it for HIV treatment. One year after delivery, the researchers saw no significant differences in hip or spine bone density in the mothers or spine bone density in the infants (hip not tested) according to DXA scans. They concluded that any bone loss that might have occurred with short-term tenofovir use was not evident at 12 months. (A newer formulation, tenofovir alafenamide or TAF (Vemlidy), is equally effective against HBV and HIV, but with fewer adverse effects on the bones and kidneys.)
"In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of tenofovir DF did not result in a significantly lower rate of transmission," the researchers concluded.
The authors noted that the HBV transmission rate in the placebo arm was low, as prior studies have seen HBV transmission rates of 7% or higher among infants born to mothers with high HBV DNA levels, despite using HBIG and HBV vaccine prophylaxis. Addition of tenofovir, therefore, could potentially be beneficial for pregnant women with high HBV viral load. Tenofovir may also reduce the risk if the first infant vaccine dose is delayed after birth or if the mother undergoes amniocentesis or Caesarean delivery, they suggested. This study did not test whether tenofovir works as well as – or perhaps better than – HBIG when combined with HBV vaccination.