Longitudinal comparison of bone, growth, and biochemical markers in breastfed HIV-exposed uninfected and HIV-unexposed Ugandan children

Abstract

Due to successful maternal antiretroviral therapy (ART), pediatric HIV infections have declined, leading to a growing population of children HIV-exposed uninfected (CHEU) in Sub-Saharan Africa. However, studies report poorer growth and development in CHEU versus children HIV-unexposed uninfected (CHUU), raising concerns about maternal HIV and ART exposure, particularly Tenofovir Disoproxil Fumarate (TDF). This analysis of data from the Gumba study compares growth trajectories, bone mineral accretion, and biochemical markers of growth and bone metabolism to age 18 months in Ugandan CHEU, exposed to maternal HIV and TDF-containing ART in utero and via breastmilk (n=85), and CHUU peers (n=80). The groups had similar weight and length 2 weeks after birth (WK2), but, despite higher exclusive breastfeeding rates, CHEU had slower growth by WK14 and ~0.5 kg lower body weight and fat mass by WK26. Growth faltering occurred in both groups from WK26, with widening differences: by WK78, 59% of CHEU were stunted compared to 33% of CHUU. CHEU had lower whole-body bone mineral content and bone area at WK14 and WK26 (Pinteraction: 0.03 and 0.0003 respectively), but similar whole-body areal bone mineral density before and after size adjustment, indicating accrued bone mineral was appropriate for their slower growth. There were no group differences in biochemical markers of growth or bone formation. However, CHEU had higher C-terminal telopeptide (CTX), a marker of bone resorption, at WK14 (group difference (95% confidence interval): +50.9 (24.1)%, P <0.001) coinciding with higher maternal CTX concentrations, and at WK78 (+45.6 (28.9)%, P <0.05). These findings suggest early onset growth deficits and altered bone metabolism in CHEU by 3 months of age, possibly linked to the TDF-containing ART initiated during pregnancy and/or disruptions in bone metabolism observed in their mothers. Further studies are needed to investigate the mechanisms and long-term implications for growth and bone health in CHEU.