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.
Infants infected through mother-to-child transmission by the hepatitis B virus are at high risk of liver damage and cancer during adulthood. For pregnant women with high virus levels in their blood, the administration of immunoglobulin to their infant at birth in addition to vaccine decreases but does not eliminate the risk of infection. Because immune globulin is not widely available, this study will assess the efficacy and safety of an antiviral drug given to the mother instead of immunoglobulin to the infant to prevent mother-to-child transmission.