Immunoglobulin-free strategy highly effective for prevention of mother-to-child hepatitis B transmission in Cambodia

Keith Alcorn
Published:
22 February 2022
Peeradon payakpan/Shutterstock.com

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.

Reference

Segeral O et al. HBIg-free strategy to prevent HBV mother-to-child transmission: ANRS TA PROHM study. Conference on Retroviruses and Opportunistic Infections, abstract 28, 2022.