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Association Between Chronic Inflammation, Bone Density, and Muscle in Peripubertal Adolescents With and Without HIV
Lisha Jeena1, Rashida A Ferrand2,3, Victoria Simms3,4
1Oxford Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Background:
We aimed to investigate the effect of human immunodeficiency virus (HIV-1)-associated inflammation on bone and muscle outcomes in adolescents with HIV (AWH) and adolescents without HIV (AWOH) and, among AWH, the impact of HIV viral load and antiretroviral treatment (ART) duration.
Methods:
AWH (on ART ≥2 years) and AWOH aged 8-16 years were enrolled. Luminex technology quantified the biomarkers C-reactive protein (CRP), soluble CD14 (sCD14), TNF-α, IL-6, IL-17, IL-18, IL-10, and IFN-γ-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] years; 49.6% female) and 287 AWOH (mean age, 12.7 [SD, 2.5] years; 50.4% female). Increased component 1 driven by IL-18, CRP, sCD14, and TNF-α 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 0.15 [95% CI, .01-.29]; P = .036); this was driven by IL-18 that was positively associated with LS-BMAD (0.90 [95% CI, .26-1.55]; P = .013) and TBLH-BMCLBM (0.72 [95% CI, .14-1.30]; P = .043) Z-scores. Biomarkers were not associated with HIV viral load, ART duration, or any muscle outcomes.
Conclusions:
Biomarkers (IL-18, CRP, sCD14, TNF-α) 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.
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