Systemic biological mechanisms underpin poor post-discharge growth among severely wasted children with HIV

Abstract In sub-Saharan Africa, children with severe malnutrition (SM) and comorbid HIV (HIV-SM) have substantially worse outcomes than children with SM alone, facing higher mortality risk and impaired nutritional recovery post-hospitalisation. The underlying biological mechanisms underpinning this risk remain incompletely understood. This case-control study nested within the CHAIN cohort in Kenya, Uganda, Malawi and Burkina Faso examined proteomic signatures associated with HIV and their impact on post-discharge growth in severely wasted children. Using the SomaScan® assay, 7335 human plasma proteins were quantified. Linear mixed models identified HIV-associated biological processes and their associations with post-discharge growth. Using structural equation modelling, we examined directed paths explaining how HIV influences post-discharge growth. HIV was associated with increased complement activation and decreased insulin-like growth factor receptor signalling and bone mineralization. HIV indirectly affected post-discharge growth by influencing baseline anthropometry and also modulating bone mineralization, humoral immune responses and other processes. These findings suggest specific biological pathways linking HIV to poor growth, offering insights for targeted interventions in this vulnerable population.