Tenofovir Disoproxil Fumarate Shows Long-Term Safety in Infants

At 192 weeks of age, infants with fetal exposure to tenofovir disoproxil fumarate (TDF) had normal physical growth, bone mineral density (BMD), and neurodevelopment. These findings were based on a study published in Gut.

TDF therapy during the third trimester of pregnancy in mothers with chronic hepatitis B (CHB) reduces the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). However, data on the physical and neuromental development of infants after fetal exposure to TDF are currently limited. Additionally, the long-term safety of TDF remains unclear. Based on the aforementioned gaps, a group of researchers sought to investigate the safety of TDF therapy during the third trimester.

From March 2012 to June 2013, 200 eligible mothers were enrolled in a randomized controlled trial (RCT) (ClinicalTrials.gov identifier: NCT01488526) in China. This study was conducted to explore the efficacy and safety of maternal TDF therapy for the prevention of MTCT in mothers with high HBV deoxyribonucleic acid (DNA) levels.

For this current study, infants from the aforementioned RCT were recruited for long-term follow-up (LTFU). Mothers with chronic hepatitis B during the third trimester were randomized to the TDF therapy group (n=92) or the control group (n=88). The Bayley-III assessment was utilized to assess infants’ physical growth or malformation, BMD, and neurodevelopment at 192 weeks of age. The primary outcome was the incidence of congenital defects or malformation occurring from birth to 192 weeks of age.

Among the 180 eligible infants; 176/180 (98%) were enrolled and 145/176 (82%) completed the LTFU (TDF-treated group: 70, control group: 75).

The mean time of fetal exposure to TDF was 8.56+0.53 weeks before birth in the TDF-treated group.   

At week 192, congenital malformation rates were similar between the TDF-treated group and the control group.

The mean body weights of boys in the control group were significantly higher compared with the TDF-treated group at 192 weeks of age (19.84±3.46 kg vs. 18.48±2.35 kg; P =.03). However, the mean body weights of boys in the TDF-treated group at week 192 were within the normal range when compared with the national standard for boys of the same age (18.48±2.35 kg vs. 17.80±2.50 kg; P =.07).

The following pre-specified outcomes were all comparable between the TDF-treated group and the control group: head circumference, height, BMD, and cognitive, motor, social–emotional, and adaptive behavior measurements.

This study is not without limitations. Further studies are needed to investigate the relationship between fetal exposure and TDF and to establish the safety of fetal exposure to TDF beyond 12 weeks.  

These findings establish the long-term safety of TDF during the third trimester for the prevention of MTCT of HBV.

“The antiviral treatment for these mothers is a particularly important method in the prevention of MTCT, which is one of the critical steps proposed by the World Health Organization (WHO) for the global elimination of HBV infection by 2030,” the study authors wrote.

Disclosure: One study author declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.

Disclosure: This research was supported by Gilead Sciences. Please see the original reference for a full list of disclosures.

Reference

Pan CQ, Dai E, Duan Z, et al. Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China. Gut. Published online March 31, 2021. doi: 10.1136/gutjnl-2020-322719