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TAF and TDF Safe, Effective for
Pregnant Mothers With HBV and Infants
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AASLD, The Liver Meeting, November 12-15, 2021
Mark Mascolini
A 207-woman nonrandomized comparison of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) in pregnant women with active chronic HBV infection confirmed overall safety of the two nucleotide analogs for both mothers and newborns [1]. Despite two virologic breakthroughs during pregnancy in women taking TAF, the mother-to-child transmission rate was 0.
Because scant data offer insight into the effectiveness and safety of TAF to prevent perinatal transmission of HBV in women with chronic HBV infection, researchers from the First Affiliated Hospital of Zhengzhou University and colleagues at other centers undertook this ongoing study. They enrolled women more than 20 year old with newly diagnosed active chronic HBV infection at any time in pregnancy. Women could have a previous chronic HBV diagnosis treated with non-TAF agents, including TDF, and women could switch to TAF or TDF for this study. The trial excluded women with inactive HBV infection, other factors that may boost alanine aminotransferase (ALT), coinfection with another hepatitis virus or HIV, evidence of hepatocellular carcinoma, cirrhosis, or systemic disorders, or current treatment with immune modulators, cytotoxic agents, or steroids.
Among 103 women in the TAF group, 69 had never taken anti-HBV therapy and 34 switched from other medications, usually entecavir (85%). Among 104 women making up the TDF group, 63 were starting their first anti-HBV agents, and 41 switched from another drug or continued TDF. Among women in the switchover or continuation group, 73% switched from entecavir.
Maternal age averaged 28.8 years in the previously untreated TAF group, 30.5 in the TAF switchover group, 29.1 in the previously untreated TDF group, and 29.8 in the TDF switchover or continuation group. Percentages of women with hemoglobin below 110 g/L in those 4 groups were 14.5%, 2.9%, 14.3%, and 4.9%. Respective proportions of women in those four groups positive for HBeAg (indicating active HBV replication) were 85.5%, 67.6%, 90.5%, and 75.6%. Across those four groups HBV DNA log10 IU/mL averaged 7.3, 0.5, 7.2, and 0.6, and ALT U/L averaged 171.6, 22, 141.3, and 22.8.
Infants received standard immunoprophylaxis including 100 IU of HBIG and three doses of recombinant HBV vaccine. At birth newborns had been exposed to TAF for an average 32.4 weeks or to TDF for an average 33.8 weeks. About one third of infants in both groups were delivered by cesarean section. There were no congenital defects or malformation at birth in either the TAF group or the TDF group. Ultrasound performed at 22 weeks and 3 days of pregnancy in 1 woman taking TAF for about 10 weeks detected cleft lip and palate in utero. A week later the woman decided to have induced abortion. Because lip and palate development processes are completed by 6 to 10 weeks of embryogenesis, the researchers concluded that this malformations could not be attributed to TAF.
In women the most frequent adverse events were nausea (29.1% with TAF, 31.7% with TDF), anorexia (22.3% with TAF, 20.2% with TDF), and fatigue (18.4% with TAF, 19.2% with TDF). Maternal complications during treatment included premature membrane rupture (12.6% with TAF, 13.5% with TDF), preterm labor (2.9% with TAF, 3.8% with TDF), and gestational hypertension (2.9% with TAF, 3.8% with TDF). The most frequent abnormal conditions in infants were prolonged jaundice (12.7% with TAF, 13.4% with TDF), and fever (12.7% with TAF, 12.5% with TDF). One infant in the TAF group had cutaneous hemangioma reported at 4 weeks of age and cured at 1 year.
Anthropometric indices in infants at birth and 7, 12, and 18 months of age did not differ significantly between the TAF and TDF groups.
Among previously untreated women HBV DNA could not be detected ("target not detected") in about half of women taking either TAF or TDF at delivery, in about 90% in both groups at postpartum month 6, and in 100% of women in both groups at postpartum months 12 and 18. In switchover or continuation groups, virtually all women had undetectable HBV DNA ("target not detected") from delivery through 18 months postpartum.
Two women taking TAF had virologic breakthroughs during pregnancy. Both women had been taking entecavir when they entered the trial. One woman began TAF 2 weeks before pregnancy and one started TAF 11 weeks before pregnancy. Respective breakthrough times were 24 weeks gestation and 25 weeks gestation. Researchers rated their adherence to therapy excellent.
Maternal HBeAg seroconversion rates were similar with TAF and TDF in previously untreated women (22.0% and 21.1%) and in women switching or continuing treatment (30.4% and 29.0%).
Seven months after delivery, no infant tested positive for hepatitis B surface antigen (HBsAg), a result indicating no HBV transmissions.
Reference
Zeng QL, et al. Tenofovir alafenamide used throughout pregnancy in Chinese active chronic hepatitis B mothers: a multicenter prospective study. AASLD, The Liver Meeting, November 12-15, 2021. Parallel session 1: Advances with Approved HBV Therapies.
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