Tenofovir may help prevent mother-to-child hepatitis B transmission

Liz Highleyman
Published:
11 October 2013

Taking tenofovir (Viread) during the final months of pregnancy may provide extra protection against perinatal transmission of hepatitis B virus (HBV) along with immunisation of the infant, according to a late-breaker presentation on Saturday at the IDWeek 2013 conference in San Francisco.

In countries where hepatitis B is endemic – including much of Asia, the Middle East and Africa – HBV is often transmitted from mother to child during pregnancy or delivery. Immediate vaccination of infants and administration of an antibody preparation, hepatitis B immune globulin (HBIG), dramatically reduces transmission risk, but it can still occur if the mother has a high HBV viral load.

Alper Gunduz and colleagues from Hamidiye Sisli Etfal Education and Research Hospital in Istanbul evaluated the safety and efficacy of tenofovir taken during the last trimester of pregnancy, along with HBV immunisation, to reduce perinatal HBV transmission from hepatitis B 'e' antigen (HBeAg)-positive women with high viral load. Prior research indicates that 10 to 30% of babies born to such women develop chronic hepatitis B despite standard prophylaxis.

This prospective analysis included 14 pregnant women referred to the researchers' clinic between June 2010 and June 2013. Most were in their twenties or early thirties. Women with hepatitis A or C or HIV co-infection and those with pregnancy complications were excluded.

The women had chronic hepatitis B infection, were hepatitis B surface antigen (HBsAg) and HBeAg-positive, and had high HBV DNA levels (greater than ten million copies/ml at baseline); most had viral loads exceeding one billion copies/ml. All had previously given birth to at least one child infected with HBV despite the use of HBIG and infant HBV vaccination.

Two women had elevated alanine aminotransferase (ALT) liver enzyme levels at baseline. The same two had previously been unsuccessfully treated with lamivudine (3TC, Epivir) or entecavir (Baraclude). Levels of creatinine, a biomarker of impaired kidney function, were normal – important because tenofovir can cause kidney toxicity in susceptible individuals.

All women received tenofovir at a dosage of 300mg once daily (the same dose used for hepatitis B or HIV treatment) starting at 28 weeks of gestation at the earliest (median 30 weeks) and continuing until delivery. All but three had caesarean sections, which can further reduce transmission risk.

In addition, all infants received 0.5ml HBIG within 12 hours after birth, plus the first injection of the recombinant HBV vaccine series, with booster shots given one and six months later.

Tenofovir treatment led to a marked reduction in mothers' plasma HBV DNA levels prior to delivery. Mean viral load declined significantly, from more than one billion copies/ml at baseline to approximately 70,000 copies/ml before delivery.

Tenofovir was generally safe and well tolerated. None of the women experienced serious adverse events due to tenofovir, including creatinine elevation. At delivery all women had ALT within the normal range. They were followed after delivery to monitor for ALT flares, which can occur when tenofovir is discontinued. None experienced post-treatment ALT elevations more than five-fold higher than baseline or more than ten-fold above the upper limit of normal. 

All 14 infants were live-born with no complications or birth defects. All the babies were breastfed. All tested negative for hepatitis B surface antigen and positive for anti-HBs antibodies at 28 to 32 weeks after birth, indicating they remained uninfected. 

"Our results suggest that [tenofovir] used during the thırd trimester of pregnancy in HBeAg-positive highly viremic mothers with simultaneous administration of HBIG and HBV vaccine to the newborns can safely prevent perinatal HBV transmission," the researchers concluded. "Prospective and larger studies are needed to confirm these findings."

With such a small study population, it is possible that none of the women would have transmitted HBV without tenofovir, though all had done so before despite standard prophylaxis. But the findings do offer reassurance that tenofovir during pregnancy is safe for mothers and babies and may provide an extra level of protection.

Reference

Gunduz A et al. Tenofovir disoproxil fumarate as an adjunctive therapy for the prevention of vertical transmission of hepatitis B virus infection. IDWeek 2013, San Francisco, abstract LB-6, 2013. View the abstract on the IDWeek website.

View the slides from the presentation.