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.
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
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
given birth to at least one child infected with HBV despite the use of
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
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
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.