www.hivandhepatitis.com

IDWeek 2013: Tenofovir May Help Prevent Mother-to-child Hepatitis B Transmission

Taking tenofovir (Viread) during the final months of pregnancy may provide extra protection against perinatal transmission of hepatitis B virus (HBV), along with immunization of the infant, according to a late-breaker presentation the Second IDWeek conference last week 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 immunization, 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 coinfection and those with pregnancy complications were excluded

The women had chronic hepatitis HBV infection, were hepatitis B surface antigen (HBsAg) and HBeAg positive, and had high HBV DNA levels greater than 10 million copies/mL at baseline; most had viral loads exceeding 1 billion copies/mL. All had previously given birth to at least 1 child infected with HBV despite the use of HBIG and infant HBV vaccination.

At baseline, 2 women had elevated alanine aminotransferase (ALT) liver enzyme levels. The same 2 had previously been unsuccessfully treated with lamivudine (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 300 mg 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 3 had Cesarean sections, which can further reduce transmission risk.

In addition all infants received 0.5 mL HBIG within 12 hours after birth plus the first injection of the recombinant HBV vaccine series, with booster shots given 1 at 6 months later.

Results

• Tenofovir treatment led toa marked reduction in mothers' plasma HBV DNA levels prior to delivery.
• Mean viral load declined significantly, from 9.12 log₁₀ (more than 1 billion) copies/mL at baseline to 4.89 log₁₀ (about 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 >5-fold higher than baseline or >10-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 infants 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.

10/8/13

Reference

A Gunduz, DY Sevgi, AS Konuklar, et al. Tenofovir disoproxil fumarate as an adjunctive therapy for the prevention of vertical transmission of hepatitis B virus infection. 2nd ID Week Conference (IDWeek 2013). San Francisco. October 2-6, 2013. Abstract LB-6.