Abstract
HIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD. Case--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility. Cryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD. Biomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association. HCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.
Highlights
The widespread use of combination antiretroviral therapy (ART) has led to a growing number of children with perinatally-acquired HIV infection (PHIV) in sub-Saharan Africa (SSA) surviving into adolescence and beyond [1]
HIV associated chronic lung disease (HCLD) was associated with a large number of soluble biomarkers representing a range of different pathways
Our findings suggest a prominent role for T-cell and platelet activation in HCLD
Summary
The widespread use of combination antiretroviral therapy (ART) has led to a growing number of children with perinatally-acquired HIV infection (PHIV) in sub-Saharan Africa (SSA) surviving into adolescence and beyond [1]. A range of chronic cardiovascular, respiratory, musculoskeletal and neurocognitive comorbidities have been described among children growing up with HIV, despite ART [2,3,4,5]. While ART has reduced the incidence of pulmonary infections, there remains a substantial burden of chronic respiratory symptoms among children and adolescents with HIV [6,7,8]. HIV associated chronic lung disease (HCLD) is typically characterised by a chronic cough, exercise restriction, hypoxia and airflow obstruction without reversibility [9]. Immune activation and inflammation are key mechanisms in the pathogenesis of multiple chronic complications of adult HIV, and are associated with airflow obstruction in HIV infected adults [10,11,12]. Either directly due to HIV infection or infections that occur as a consequence of HIV-related immunosuppression may result in progressive tissue remodeling, fibrosis of the small airways and lung function decline [13]
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