Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe

Background: Poor linear growth and pubertal delay, both common in children with HIV (CWH) in sub-Saharan Africa, may affect adolescent bone accrual and future fragility fracture risk. We investigated the association of HIV with size-adjusted bone density in peri-pubertal children in Zimbabwe.
Methods: CWH aged 8-16 years taking ART for ≥2 years from public-sector HIV clinics in Harare, and HIV-uninfected children from schools in the same suburbs, were recruited into a cross-sectional study. Sociodemographic, clinical and anthropometric data were collected. The prevalence of dual-energy X-ray absorptiometry (DXA) measured bone outcomes, total-body less-head bone mineral content-for-lean mass adjusted for height (TBLH-BMCLBM) and lumbar spine bone mineral apparent density (LS-BMAD), were determined. Linear regression models, using multiple imputation for missing data, assessed relationships between risk factors and TBLH-BMCLBM and LS-BMAD Z-scores. 
Findings: We recruited 303 CWH and 306 without HIV, mean (SD) age 12.5 (2.5) years and 50% female. Median ART duration was 8.1 (IQR 6.2-9.5) years; for 102 (34%) ART included tenofovir disproxil fumarate (TDF). Compared to children without HIV, those with HIV had higher prevalence of TBLH-BMCLBM (10.4% vs. 6.2%, p=0.066) and LS-BMAD Z-Scores <-2 (14.3% vs. 5.8%, p=0.001). HIV and male sex were associated with earlier Tanner stage. The negative associations between HIV and both TBLH-BMCLBM and LS-BMAD were more pronounced with pubertal maturation, particularly in females. Among CWH, years of TDF exposure and orphanhood were associated with lower TBLH-BMCLBM Z-Score. Current TDF use (v.s., non-TDF containing ART) was associated with a reduction in TBLH-BMCLBM and LS-BMAD Z-Scores of 0.41 (95%CI 0.08, 0.74; p=0.015) and 0.31 (0.08, 0.69; p=0.116) respectively.Interpretation: Despite ART, HIV is associated with substantial skeletal deficits towards the end of puberty. The size of bone deficits associated with TDF and its widespread use in children in sub-Saharan Africa raise concern for future adult fracture risk.