Biochemical Markers of Calcium and Bone Metabolism During and After Lactation in Ugandan Women with HIV on Universal Maternal Antiretroviral Therapy.

We reported accentuated lactational decreases in areal bone mineral density and only partial skeletal recovery post-lactation in Ugandan women with HIV (WWH) initiated onto tenofovir disoproxil fumarate-based antiretroviral therapy (TDF-based ART) during pregnancy compared to women without HIV (REF). WWH also had higher breast milk calcium in first months of lactation. To investigate mechanisms, we measured bone turnover markers (bone resorption: C-terminal telopeptide (CTX); bone formation: procollagen type 1 N-terminal-propeptide (P1NP), bone-specific and total alkaline phosphatase (BALP, TALP)), hormones (parathyroid hormone (PTH), intact fibroblast growth factor 23 (FGF23), 1,25-dihydroxyvitamin D (1,25(OH) 2 D)), vitamin D status (25-hydroxyvitamin D (25OHD)) and indices of mineral metabolism and renal function. Blood and urine samples collected at 36 weeks gestation, 14- and 26-weeks lactation and 3-6 months post-lactation were analysed. Mean 25OHD was >50 nmol/L throughout. Both groups experienced similar biochemical changes during pregnancy and lactation to women in other settings but, within these patterns, the two groups differed significantly. Notably, WWH had higher PTH (+31%) and lower 1,25(OH) 2 D (-9%) and TmP/GFR (-9%) throughout, lower P1NP (-27%) and plasma phosphate (-10%) in pregnancy, higher CTX (+15%), BALP (+19%) and lower eGFR (-4%) during and after lactation. P1NP/CTX ratio was lower in WWH than REF in pregnancy (-21%), less so in lactation (-15%) and similar post-lactation. Additionally, WWH had lower plasma calcium (-5%), lower FGF23 (-16%) and fasting urinary calcium (-34%) at one or both lactation timepoints, and higher fasting urinary phosphate (+22%) at 26 weeks lactation and post-lactation. These differences resemble reported TDF effects, especially raised PTH, increased bone resorption, decreased bone formation and decreased renal function, and may explain the observed differences in bone mineral density and breast milk calcium. Further studies are needed to determine whether HIV and TDF-based ART have long-term consequences for maternal bone health and offspring growth. This article is protected by copyright. All rights reserved.