Association between chronic inflammation, bone density and muscle in peripubertal adolescents with and without HIV in Zimbabwe: a cross-sectional study

Background To investigate the effect of HIV-associated inflammation on bone and muscle outcomes in adolescents with (AWH) and without HIV (AWOH), and, among AWH, the impact of HIV viral load and ART duration. Methods AWH (on ≥2 years antiretroviral treatment (ART)) and AWOH aged 8-16 years were enrolled. Luminex® technology quantified biomarkers CRP, sCD14, TNFα, IL-6, IL-17, IL-18, IL-10, and IFNγ- chosen based on their relevance to HIV, bone and muscle. Factorial analysis of mixed data reduced measurements into components. Sex-stratified adjusted linear regression assessed associations between HIV status and biomarker components, HIV-related factors (viral load and ART duration) and components, and components and bone/muscle outcomes. Where associations were found, individual biomarkers were investigated. Outcomes included height-adjusted-total-body-less-head-bone-mineral-content-for-lean-mass (TBLH-BMCLBM) and size-adjusted-lumbar-spine-bone-mineral-apparent-density (LS-BMAD) Z-scores, TBLH-lean-mass, grip strength and lower-limb power. Results There were 270 AWH (mean age 12.6[SD 2.5], 49.6% female) and 287 AWOH (12.7[2.5], 50.4% female). Increased component 1 driven by IL-18, CRP, sCD14, TNFα was associated with HIV status. Unexpectedly, among girls with HIV, higher component 1 was associated with greater LS-BMAD Z-score (adjusted mean difference β-coefficient[95% confidence interval] 0.15[0.01, 0.29], p=0.036); this was driven by IL-18 that was positively associated with LS-BMAD (0.90[0.26; 1.55], p=0.013) and TBLH-BMCLBM (0.72[0.14; 1.30], p=0.043) Z-scores. Biomarkers were not associated with HIV viral load, ART duration nor any muscle outcomes. Conclusion Biomarkers (IL-18, CRP, sCD14, TNFα) were increased in AWH and may be linked to higher bone density in girls with HIV. IL-18 plays an important role on bone that has not been previously described and warrants further investigation.