A hepatitis B immunuglobulin-free
strategy for prevention of mother-to-child hepatitis B transmission is feasible
and highly effective in a resource-limited setting if tenofovir is given for at
least four weeks prior to delivery, a team of French and Cambodian researchers
reported last week at the 2022 Conference on Retroviruses and Opportunistic
Infections (CROI).
Reducing
mother-to-child transmission of hepatitis B is a critical element in efforts to
eliminate hepatitis B.
Perinatal
prophylaxis against mother-to-child transmission of hepatitis B consists of
infant vaccination against hepatitis B within 24 hours of birth, along with
infusions of hepatitis B immunoglobulin G (HBIgG) for the infant after birth,
to provide antibody protection until the infant’s own response begins to produce
antibodies after vaccination.
For mothers,
tenofovir is recommended if hepatitis B DNA levels are above 5.3 log 10 IU/ml
during the last trimester, and/or the mother is hepatitis B ‘e’ antigen positive
(HBeAg+) (a sign of viral replication).
But for lower-income
countries like Cambodia, this strategy can be challenging to implement due to
limited health system resources. Lack of access to hepatitis B immunoglobulin G
and HBV DNA testing prevents timely provision of either HBIgG or tenofovir.
Immunoglobulin-free
alternative regimens are needed, as well as a point-of-care rapid test for hepatitis
B ‘e’ antigen as an alternative to HBV DNA quantification.
The TA-PROHM
study was designed to test a strategy that could address these gaps. The study intervention consisted of three elements:
- The use of rapid diagnostic tests for
hepatitis B surface antigen and ‘e’ antigen, together with ALT, in an algorithm
to determine which women needed tenofovir prophylaxis in the last trimester of
pregnancy.
- Tenofovir prophylaxis from week 24 of pregnancy
until 6 weeks postpartum for those eligible.
- Infant vaccination against hepatitis B within
two hours of delivery and at weeks 6, 10 and 14.
The TA-PROHM study was a single arm study conducted between 2017
and 2020 at five maternity hospitals in Cambodia. The study enrolled pregnant
women who tested HBsAg-positive. Participants were assigned to receive
tenofovir if they tested HBeAg-positive up to January 2019, when the study protocol
was revised so that women who tested negative for HBeAg were eligible to receive
tenofovir if they had an ALT measurement of 40 IU/ml or above.
During the study period, 21,251 women were screened for HBsAg,
1194 tested positive and were included in the study. Twenty-eight per cent (338)
were eligible for tenofovir treatment and 317 initiated tenofovir and gave
birth at study sites. Of those not eligible for tenofovir (856), 746 gave birth
at study sites.
In 324 infants born to tenofovir-eligible mothers, 13% received HBIgG
at birth, 88% received hepatitis B vaccine within two hours of birth and 97%
within 24 hours of birth. In 752 infants born to tenofovir-ineligible mothers,
16% received HBIgG at birth, 87% received hepatitis B vaccine within two hours
of birth and 96% within 24 hours of birth.
The primary study outcome was the proportion of infants testing hepatitis
B surface-antigen-positive six months after birth, stratified by HBIgG exposure
and maternal tenofovir treatment duration of four week or less.
In 317 infants born to tenofovir-eligible mothers and tested for
HBsAg at six months of age, four (1.26%) tested positive for HbSAg. Three mothers
had received tenofovir for less than four weeks prior to delivery and one mother had not taken
tenofovir. No hepatitis B transmission took place to infants when mothers had
taken tenofovir for at least four weeks prior to delivery and all positive HBsAg results in the
tenofovir-eligible group occurred in the 271 infants that did not receive HBIgG
(1.4% positivity rate among HbIgG non-exposed).
In 712 infants born to tenofovir-ineligible mothers, seven tested positive
for HbsAg (0.98%). Six of the seven had not received HBIgG (1.06% positivity
rate among HbIgG non-exposed).
Ninety-four per cent of tenofovir-eligible women started tenofovir
and 78% reported adherence of at least 90% at each study visit. At delivery,
50% of those who took tenofovir for less than four weeks and 89% who took
tenofovir for four weeks or more had hepatitis B DNA levels of 5.3log10 IU/ml
or below at delivery.
Grade 3 or 4 adverse events occurred more frequently in tenofovir-eligible
women (13% vs 5%) and this difference was largely driven by a higher rate of
liver-related grade 3 or 4 events in tenofovir-eligible women (12% vs 2%).
Rates of adverse events were similar between study arms in infants (5% vs 4%).
Study investigator Olivier Segeral said that the transmission rate
observed in this study was similar to those in randomised studies which combined
HBIgG and tenofovir. The critical factor appeared to be the duration of
treatment; no transmission occurred if women had been treated for at least four
weeks prior to delivery, whereas the transmission rate women treated for less than four weeks was
8%, emphasising the importance of early screening and prompt initiation of tenofovir.