Simplified tenofovir regimen as effective as recommended preventive treatment in pregnant women with hepatitis B

A simplified regimen for the prevention of mother-to-child transmission of hepatitis B was just as effective as the standard preventive regimen in pregnant women with very high virus levels and is likely to prove easier to implement in resource-limited settings, Professor Calvin Pan of New York University Grossman School of Medicine reported at the AASLD Liver Meeting last week.

He was presenting results of a clinical trial carried out at seven major hospitals in China, where vertical transmission of hepatitis B remains a significant challenge.

The US-recommended regimen for the prevention of vertical transmission consists of maternal treatment with the antiviral tenofovir disoproxil fumarate (TDF) from week 28 of pregnancy if maternal viral load is above 200,000 IU/ml, combined with infant hepatitis B vaccination at birth, with follow-up vaccine doses at weeks 4 and 24 postpartum, plus hepatitis B immunoglobulin within 12 hours of birth.

The World Health Organization recommends maternal TDF from week 28 of pregnancy if viral load is above 200,000 copies/ml, plus infant vaccination. It also recommends an infant hepatitis B immunoglobulin dose where this is available, especially in cases where the mother has a high HBV DNA level.

But WHO’s 2020 guidance recognises that it is more challenging to deliver the hepatitis B immunoglobulin dose after birth in lower-income settings, where it is costly and often in short supply. According to GAVI, the global vaccine-funding alliance, global coverage of HBV immunoglobulin is less than 13%

To test whether starting tenofovir treatment earlier in pregnancy, without using hepatitis B immunoglobulin, would prove to be as effective as standard treatment in preventing vertical transmission of hepatitis B, US and Chinese researchers carried out a randomised study.

The study recruited pregnant women who were HBeAg-positive, with hepatitis B DNA levels above 200,000 IU/ml and randomised them to receive either TDF from week 14-16 of gestation or from week 28 of gestation (control group). All infants received hepatitis B vaccine within 12 hours of birth and at weeks 4 and 24 postpartum. Infants born to mothers in the control group also received hepatitis B immunoglobulin.

The study enrolled 280 women. Two hundred and sixty-five mothers and 269 infants completed the study. The median baseline HBV DNA level was approximately 8 log₁₀ IU/ml in each study arm.

At delivery, women in the intervention arm had been taking tenofovir for a median of 23 weeks, compared to 11 weeks in the comparator arm.

There was no vertical transmission in either study arm. Women in the experimental arm had significantly lower HBV DNA levels at delivery ((2.36 log₁₀ IU/ml vs 3.63 log₁₀ IU/ml; p < 0.001) and a higher proportion had HBV DNA levels below 200,000 IU/ml (99% vs 94%, p = 0.04).

There was no significant difference in serious maternal adverse events or adverse birth outcomes between the study arms.

The study investigators concluded that the intervention regimen was equivalent to the current standard of care and that the preventive regimen can be simplified safely, so that HBV immunoglobulin does not need to be used in resource-limited settings.