ARTFUL AGEING: Investigating ageing mechanisms in children growing up with HIV in the era of antiretroviral therapy

We will determine how the mechanisms underlying biological ageing limit trajectories of growth, physical and cognitive function in children growing up with HIV. Despite antiretroviral therapy (ART) successes, children with HIV (CWH) commonly experience multi-system comorbidities limiting growth, physical and cognitive function, with phenotypes reminiscent of those seen in older adults. In older adults, Geroscience has identified a discrete set of hallmarks of biological ageing (primary, antagonistic and integrative) responsible for a common systemic susceptibility to disease. We hypothesize that perinatally-acquired HIV infection causes Accelerated Biological Ageing in children which drives poorer long-term health and development. Within a 24-month prospective cohort study recruiting 800 children aged 6-9 years in Harare (400 CWH on ART, and 400 HIV-negative and unexposed), our objectives are to: 1. Quantify domain-specific deficits (growth, physical, cognitive) in CWH, compared to their uninfected peers, longitudinally. 2. Characterise hallmarks of biological ageing in children with and without HIV. 3. Determine the role of accelerated hallmarks of biological ageing in explaining domain-specific deficits longitudinally in CWH. 4. Identify gero-protectors and gero-drivers potentially amenable to future therapeutic interventions. Our innovative South-North consortium melds HIV physicians, paediatricians, geriatricians and experts in geroscience to ‘Discover the Science’ behind paediatric HIV-associated ageing.