A US cohort study (CID 2015;61:996) reported 12% lower newborn mean bone mineral content (BMC) after maternal tenofovir disoproxil fumarate (TDF) use.
The P1084s substudy sought to compare newborn BMC by exposure to maternal antiretroviral (ARV) regimens at >14 weeks gestational age (GA) randomly assigned in the IMPAACT PROMISE trial: Arm 1: zidovudine[ZDV] (+ single-dose nevirapine+ TDF/emtricitabine[FTC] tail); Arm 2: ZDV/lamivudine/lopinavir-ritonavir[LPVr]; Arm 3: TDF/FTC/LPVr. Infants underwent whole-body (WB) and lumbar spine (LS) dual-energy X-ray absorptiometry (DXA) BMC measurements by age 28 days at 8 African sites equipped and trained for infant DXA scans. Standardized scan analysis was performed centrally. The accrual target of 150 infants per Arm was based on 80% power to detect a pair-wise difference of 4-5% in mean WB-BMC and 6-7% in mean LS-BMC. Maternal and infant characteristics were compared with Fisher’s exact, Chi-square or Kruskal-Wallis tests, as appropriate. Mean BMC differences were compared with Student’s t-test. Because mothers enrolled in the substudy after randomization, we used multivariable linear regression to adjust for baseline maternal factors and infant factors at time of DXA scan.
Of 452 eligible mothers, data from 425 infants remained for analysis after accounting for twins(6), fetal (8) or neonatal death(10) and drop-outs(15). Mothers differed across Arms on age (median 25 vs 27 vs 27 years, p=.008). Newborns differed in birth weight (median 3090 vs 2900 vs 2900g, p<.001) and weight-for-length Z-score (mean -0.4 vs -0.8 vs -0.8, p=.032) but not GA (median 39 weeks for all Arms, p=.264) or birth length (median 49cm for all Arms, p=.327). By Arm, mean LS-BMC were 1.73 vs. 1.64 vs 1.72g and WB-BMC were 73.1 vs. 65.1 vs. 63.3g. Pairwise comparisons revealed no significant differences between Arms 2 and 3 (primary objective) for LS- and WB-BMC but significantly lower mean WB-BMC in Arms 2 and 3 compared to Arm 1, which persisted after adjustment (Table). Differences of borderline significance emerged in some pairwise comparisons of LS-BMC when adjusted for maternal or maternal and infant factors.
No adverse infant BMC effect was linked to maternal TDF use. Initiation of a triple-ARV, LPVr-containing regimen during pregnancy may lead to lower newborn bone mineralization.