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HBIg-Free Strategy Prevents Vertical HBV Transmission-If Mothers Start TDF Soon Enough
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2022 CROI, February 12-16 and 22-24, 2022
Mark Mascolini
A strategy to prevent vertical transmission of HBV that does not include hepatitis B immune globulin (HBIg)* worked in a large Cambodian study-as long as mothers started tenofovir disoproxil (TDF) at least 4 weeks before delivery and neonates got the HBV vaccination promptly after birth [1]. Because the strategy does not depend on HBIg, ANRS researchers said, it could allow decentralization of HBV transmission prevention to rural areas where most pregnant women get care in Cambodia.
According to the ANRS team, HBV infection prevalence stands at an estimated 4% in pregnant women in Cambodia-and at 10% in infants born to mothers positive for hepatitis B surface antigen (HBsAg), which indicates active HBV infection. In Cambodia and other countries vertical HBV prevention relies on vaccinating all infants within 24 hours of birth, HBIg for infants at birth, and maternal TDF in the third trimester of pregnancy if HBV DNA lies above 5.3 log10 IU/mL. But Cambodia and similar countries cannot readily get HBIg because of high cost and structural barriers. HBV DNA assays may also be hard to come by in low-income countries, so an HBeAg rapid diagnosis test (RDT) may have to be used instead.
Researchers at the University of Health Sciences in Phnom Penh and collaborators at other centers planned this analysis, the ANRS TA PROHM study, to assess the effectiveness of an HBIg-free strategy to prevent vertical HBV transmission in Cambodia. The strategy has three parts: (1) an HBsAg/HBeAg RDT and an alanine aminotransferase (ALT)-based algorithm to screen pregnant women and decide on TDF prophylaxis, (2) TDF treatment for eligible women from 24 weeks of gestation or immediate treatment for eligible women seen later, and (3) vaccination of all infants within 2 hours of birth. The primary outcome was the percentage of HBsAg-positive infants at 6 months of age stratified by infant HBIg status and whether the mother got TDF for at least 4 weeks.
This single-arm prospective trial ran from October 2017 to November 2020 in 5 maternity units in Cambodia. Researchers enrolled HBsAg-positive women screened during antenatal care with an HBeAg RDT. Women became eligible for TDF if HBeAg-positive on the RDT (October 2017 to December 2018) or HBeAg-positive or negative on the RDT with an ALT at or above 40 IU/L (from January 2019). Infants got vaccinated at birth and weeks 6, 10, and 14. HBIg could be used if available, and only 1 of 5 units used HBIg.
Researchers screened 21,251 women, 1326 tested positive for HBsAg, and 1194 got included in the study. Of women included, 338 (28%) were eligible for TDF and 856 (72%) were not. Six months after delivery, 317 infants in the maternal TDF-eligible group and 712 in the TDF-ineligible group got tested for HBsAg. More than 96% of infants got the HBV vaccine within 24 hours of birth. A median 15 minutes passed between birth and vaccination.
At 6 months of age among all infants, 1.26% (95% confidence interval [CI] 0.34 to 3.20) born to TDF-eligible mothers tested positive for HBsAg, compared with 0.98% (95% CI 0.40 to 2.02) for infants of TDF-ineligible mothers (difference not statistically significant). Among infants who did not get HBIg, respective HBsAg-positive rates were 1.48% (95% CI 0.40 to 3.74) and 1.06% (95% CI 0.39 to 2.30) (not statistically significant). In infants who did not get HBIg, none were HBsAg-positive if their mother got TDF for more than 4 weeks (95% CI 0.00 to 1.61), 8.33% (95% CI 1.75 to 22.5) were positive if their mother got TDF for fewer than 4 weeks, and 12.50% (95% CI 0.32 to 52.65) were positive if their mother got no TDF.
Among women eligible for TDF, 94.1% started TDF, 78.8% had better than 90% adherence at every visit, and 89.8% took TDF for more than 4 weeks. Proportions of women with any grade 3 or 4 adverse event or a serious adverse event were 13.9% in the TDF-eligible group and 5.8% in the TDF-ineligible group. Respective proportions with any grade 3 or 4 adverse event or a serious adverse event related to liver cytolysis were 12.4% and 2.3%. Proportions of infants with any grade 3 or 4 adverse event or any serious adverse event were 5.9% with TDF-eligible mothers and 4.2% with TDF-ineligible mothers.
The researchers concluded that “an HBIg-free strategy with maternal use of TDF and early vaccination at birth could be effective” to prevent vertical transmission of HBV if TDF begins more than 4 weeks before delivery. Not using HBIg and using a therapeutic algorithm (HBeAg RDT/ALT) instead of an HBV DNA assay to select women eligible for TDF allows this HBIg-free strategy to be used in rural areas, where most pregnant women in Cambodia receive care.
Reference
1. Segeral O, Dim B, Durier C, et al. HBIg-free strategy to prevent HBV mother-to-child transmission: ANRS TA PROHM study. 2022 CROI, February 12-16 and 22-24, 2022. Abstract 28.
*Hepatitis B immune globulin (HBIg) is a human immunoglobulin used to prevent hepatitis B infection and to treat acute exposure to HBsAg.
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