Real-world clinical data-driven modelling on the initiation time of antiviral prophylaxis among pregnant women with chronic hepatitis B infection

Background & Aims: The risk of mother-to-child transmission for pregnant women with chronic hepatitis B (CHB) still exists, especially for those with high HBV DNA levels. The guidelines for initiating prophylaxis for pregnant women with CHB vary across countries. We aimed to explore the latest prophylaxis initiation time for these women. Methods: We collected the real-world clinical data of 328 pregnant women aged 20-49 with CHB, who were treated with telbivudine or tenofovir disoproxil fumarate, from July 2010 to December 2020 in China. A mathematical model was developed to describe the viral kinetics of HBV after prophylaxis. We calculated the time required to reduce viral load below the threshold value of 5.3 log₁₀ IU/ml. We derived the prophylaxis initiation time by subtracting the required time to threshold from the childbirth gestational week. Results: The median time for 328 women to reduce HBV DNA levels below the threshold of 5.3 log₁₀ IU/ml was 4.2 (range: 0.2-12.8) weeks, corresponding to a prophylaxis initiation time of no later than 35.1 (25.2-41.4) weeks. Specifically, for women with viral loads >8.0 log₁₀ IU/ml, prophylaxis should be initiated before 33.9 (25.2-39.5) weeks, and even before the lower bound of 25.2 weeks, to maximize clinical safety. For women with viral load >7.0 to ≤8.0 log₁₀ IU/ml, prophylaxis should be initiated before 35.5 (28.6-39.8) weeks, and for women with viral load >5.3 to ≤7.0 log₁₀ IU/ml, prophylaxis should be initiated before 36.2 (28.3-41.4) weeks. Conclusion: Pregnant women with HBV DNA levels >5.3 to ≤8.0 log₁₀ IU/ml can initiate prophylaxis before 28 gestational weeks. However, women with HBV DNA >8.0 log₁₀ IU/ml could consider initiating prophylaxis before 25 weeks. Impact and implications: This study investigates how long it takes to decrease maternal viral load below a threshold (5.3 log₁₀ IU/ml) after receiving antiviral prophylaxis in pregnant women with different HBV DNA levels based on real-world clinical data and mathematical modelling, which provides quantitative evidence on the initiation time of antiviral prophylaxis. The results show that pregnant women with CHB infection at high HBV DNA levels (>8 log₁₀ IU/ml) should initiate antiviral prophylaxis earlier to decrease the risk of mother-to-child transmission of HBV. Physicians can determine when to begin antiviral prophylaxis for those women according to their maternal HBV DNA levels. Our findings justify the initiation time of antiviral prophylaxis recommended by the Chinese guidelines and will offer new insights for other international guidelines.