Tenofovir for Preventing HBV Vertical Transmission
Trial question
Is tenofovir starting at gestational week 16 noninferior to tenofovir starting at gestational week 28 in pregnant women with HBV and high levels of viremia?
Study design
Multi-center
Open label
RCT
Population
280 female patients.
Inclusion criteria: pregnant women with HBV and high levels of viremia.
Key exclusion criteria: coinfection with HIV; HAV, HCV, HDV, or HEV, or STDs; ALT levels > 200 U/L; TBIL > 2 mg/dL; decompensated liver disease or cancer; estimated CrCl < 100 mL/min; history of kidney dysfunction or fetal abnormalities in a previous pregnancy; clinical signs of threatened miscarriage; ultrasound evidence of fetal abnormalities.
Interventions
N=140 tenofovir from gestational week 16 (tenofovir disoproxil fumarate 300 mg daily from gestational week 16 to delivery plus HBV vaccination for infants).
N=140 tenofovir from gestational age 28 (tenofovir disoproxil fumarate 300 mg daily from gestational week 28 to delivery plus HBV immune globulin and HBV vaccination for infants).
Primary outcome
Mother-to-child transmission rate
0.76%
0%
0.8 %
0.6 %
0.4 %
0.2 %
0.0 %
Tenofovir from gestational week
16
Tenofovir from gestational age
28
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in mother-to-child transmission rate (0.76% vs. 0%; AD 0.76%, 95% CI 0 to 1.52).
Secondary outcomes
Significant increase in HBV DNA levels < 200,000 IU/mL at delivery (99.2% vs. 94.2%; AD 5%, 95% CI 0.1 to 10).
Significant increase in HBV DNA levels < 20,000 IU/mL at delivery (94.7% vs. 65.9%; AD 28.8%, 95% CI 19.2 to 38.3).
No significant difference in the rate of HBeAg negativity at postpartum week 28 (2.1% vs. 2.1%).
Safety outcomes
No significant differences in frequency and severity of pregnancy or obstetric complications, grade 3 or 4 adverse events in live-born infants.
Conclusion
In pregnant women with HBV and high levels of viremia, tenofovir from gestational week 16 was noninferior to tenofovir from gestational age 28 with respect to a mother-to-child transmission rate.
Reference
Calvin Q Pan, Erhei Dai, Zhongfu Mo et al. Tenofovir and Hepatitis B Virus Transmission During Pregnancy: A Randomized Clinical Trial. JAMA. 2024 Nov 14:e2422952. Online ahead of print.
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