The vast majority of perinatal hepatitis B (HB) infections become chronic infections, causing cirrhosis and liver
cancer in adulthood. More than 250 million people (about 6% of the world's population) are chronically infected
with HB virus (HBV), causing nearly 780,000 deaths each year. Universal HB immunization, starting with a birth
dose of vaccine, is not sufficient to prevent all mother-to-child transmission, especially when mothers have high
viral loads. In such cases, administration of HB immune globulin (HBIg) is recommended in addition to vaccine.
In three studies, including a randomized clinical trial (iTAP) conducted by our group in Thailand, no transmissions
occurred when mothers received an anti-HBV antiviral treatment at the end of pregnancy and early postpartum
period. Maternal antiviral treatment decreases viral loads to those levels seen in mothers who seldom transmit
the virus. In these studies, the antiviral treatment was safe and well tolerated by the mothers and infants.
We hypothesize that HBIg can be replaced by maternal antiviral treatment for infants vaccinated at birth.
Our primary objective is to demonstrate that, when mothers with high viremia who receive antiviral prophylaxis
and when the newborn does not receive HBIg, the risk of HBV transmission to infants is less than 2%, the lowest
rate of transmission ever reported without antiviral.
This is relevant to public health given that HBIg is not widely available and most infants born to HBV infected
mothers do not receive it and that HBIg plus vaccine administered at birth cannot prevent all infections, especially
those already established in utero. This innovative strategy has never been tested in a carefully controlled setting.
We propose a multicenter, open-label, single arm, prospective clinical study in infants born to mothers with high
viremia (HBe antigen positive) who receive the antiviral tenofovir disoproxil fumarate (TDF) from 28-30 weeks
gestation until 2 months postpartum, while infants receive active immunization but no HBIg. The study will be
conducted in Thailand and Laos PDR and will enroll 439 women and their infants in 32 sites of our clinical
research network. HBsAg positive women will be enrolled if they have an HBeAg positive test (a widely available
test of high virus replication). Mothers will be followed until one year postpartum and infants 18 months. The
primary endpoint will be the detection of HBsAg confirmed by PCR detection of HBV DNA at six months of life.
Demonstrating that antiviral treatment plus vaccine is sufficient to prevent virtually all perinatal HBV
transmissions without the use of HBIg would revolutionize HBV PMTCT. The results of the study will help define
policy to manage HBV infected pregnant women with an HBeAg positive test to prevent perinatal transmission.