Tenofovir disoproxil fumarate (TDF) is increasingly used for hepatitis B virus (HBV) mono-infected pregnant women with high HBV DNA levels to prevent mother-to-child transmission (PMTCT) of HBV. In HIV infected women, TDF may adversely affect maternal and infant bone mineral density (BMD). In a sub-study of a randomized controlled trial of TDF for PMTCT of HBV, we assessed the effect of TDF on maternal and infant BMD one year after delivery/birth.
HBV chronically infected mothers were randomized to receive TDF or a matching placebo from 28 weeks gestational age (GA) to 2 months postpartum, in the iTAP study (NCT01745822) in Thailand. Breastfeeding was encouraged. Maternal hip and lumbar spine BMD and infant lumbar spine BMD were measured at 12 months after delivery/birth using dual-energy X-ray absorptiometry (DXA) at three participating sites (phantoms were circulated for cross calibration). All investigators and operators were blinded to the treatment arm. The analysis was based on DXA scans performed at sites and centrally reviewed by two experts (BF, WT) for accuracy. A sample of at least 45 mother-infant pairs per arm provided over 80% power to detect a 13.5% mean reduction in infant lumbar spine BMD in the TDF arm compared to the placebo arm (two-sided Student’s t-test, significance level 0.05).
A total of 135 mother-infant pairs (69 TDF, 66 placebo) plus 5 singleton mothers (2 TDF, 3 placebo) who did not come with their infants and 2 singleton infants (1 mother unavailable, on TDF; 1 mother pregnant, not eligible, on placebo) were included. Median (interquartile range) maternal body mass index before pregnancy was 21.1 kg/m2 (19.1 to 23.9), weight at enrollment 62 kg (56 to 71), age at enrollment 26.7 years (23.3 to 29.2) and GA at delivery 39.1 weeks (38.3 to 40.1). Of the 140 mothers, 135 breastfed for a median 6.1 months (3.8 to 12.0) and 5 did not breastfeed. BMD was assessed at a median 12.2 months (11.9 to 12.5) after delivery/birth. Infant median weight was 8.9 kg (8.2 to 9.8) and length 74 cm (72 to 76). Maternal and infant characteristics were balanced between arms. Results of maternal hip and lumbar spine BMD and infant lumbar spine BMD measurements are provided in the table.
One year after delivery/birth, there were no significant differences in maternal hip or lumbar spine BMD or infant lumbar spine BMD between arms. In the hypothesis that BMD was affected by TDF exposure, this did not persist 10 months after treatment discontinuation.