Tenofovir alafenamide (TAF; Vemlidy) is highly effective at
preventing transmission of hepatitis B virus (HBV) from mothers with a high
viral load to their infants, according to a pair of studies presented at the AASLD virtual Liver Meeting this week.
Mother-to-child transmission is the most common route of HBV infection
worldwide. The risk of transmission ranges from 70 to 90% for mothers who have
a high viral load or are hepatitis B 'e' antigen positive (HBeAg), according to the World Health Organization (WHO).
Perinatal transmission can be prevented by giving
infants their first dose of the hepatitis B vaccine immediately after birth.
The risk can be further reduced by administering hepatitis B immunoglobulin, or
injected antibodies. Yet this does not offer complete protection, especially if
the mother has a high viral load.
WHO recently updated its guidelines for prevention of perinatal HBV transmission, and now conditionally
recommends that pregnant women with a high viral load (200,000 IU/ml or
greater) should receive tenofovir prophylaxis from the 28th week of gestation
at least until the time of delivery. If HBV DNA testing is unavailable, a
positive HBeAg test can also be used to determine eligibility. After delivery,
mothers should be assessed to determine whether they could benefit from
remaining on long-term antiviral treatment.
The recommendation was based on research
showing that tenofovir disoproxil fumarate (TDF; Viread) is safe for pregnant women and their babies and can prevent
perinatal HBV transmission; however, some studies have not seen a benefit.
TAF is a newer formulation of tenofovir
that causes less kidney and bone toxicity than TDF but is associated with
higher blood lipid levels and a greater risk of weight gain.
first study, Dr Yang Ding of Shengjing Hospital of China Medical University and colleagues investigated the safety and
efficacy of TAF for the prevention of mother-to-child transmission of HBV. This
multi-centre study enrolled 71 HBeAg-positive pregnant women with HBV DNA
levels great than 200,000 IU/ml.
received TAF starting in the second or third trimester. The infants received hepatitis B immunoglobulin and the first
HBV vaccine dose at birth, with two further vaccine doses and one and six
time of delivery, 86% of the women saw a reduction in viral load. HBV DNA decreased
by an average of 3.69 log10 IU/ml,
bringing the mean level down to about 12,000 IU/ml.
the 73 infants born (including two sets of twins) completed the vaccine regimen.
Two-thirds were breastfed. All the infants tested negative for hepatitis B surface
antigen (HBsAg) and had undetectable HBV DNA (below 100 IU/ml) at six or seven
months. None of the babies had evidence of birth defects and growth parameters
including weight, height and head circumference were normal.
the mothers or infants experienced severe adverse events. However, 15% of the
women experienced ALT liver enzyme flares after delivery.
The researchers concluded
that "TAF therapy for highly viraemic mothers was well tolerated and
effectively prevented mother-to-child transmission of HBV" with no safety
concerns for mothers or infants.
second study, Dr. Qing-Lei Zeng of the
First Affiliated Hospital of Zhengzhou University and colleagues compared
outcomes among 232 pregnant women who received either TAF or TDF. The women had
HBV DNA levels above 200,000 IU/ml, more than 90% were HBeAg positive and they
had normal ALT at study entry.
A total of 116 women received TAF and 116 received
TDF from the third trimester until delivery. Here too, the infants received hepatitis B immunoglobulin and HBV vaccine
doses at birth, one month and six months.
the women experienced a decline in HBV DNA by the time of delivery, averaging
about 3000 IU/ml in the TAF group and 2500 IU/ml in the TDF group. None
achieved HBeAg or HBsAg loss (considered a functional cure).
the 117 infants born to women who used TAF or the 116 babies born to women who
used TDF tested HBsAg positive at seven months, including those who were
breastfed. Again, none of the infants had birth defects and their physical and
neurological development was normal. There were no notable differences between
babies exposed to TAF or TDF during gestation.
Both TAF and TDF were well
tolerated and none of the women stopped treatment due to adverse events. Here
too, some mothers had ALT flares at the time of delivery or postpartum.
both studies showed that TAF is safe and effective for preventing mother-to-child
transmission, cost may limit its use. TAF, from Gilead Sciences, is still under
patent, while generic versions of TDF are available in many countries for
around £2 (US$3).