Active Infection & Immunity

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

In plain English

AI plain-English summary

Children growing up with HIV in Zimbabwe are showing signs of biological ageing typically seen in older adults, despite being on effective antiretroviral therapy. This matters because these children commonly develop multiple health problems—stunted growth, poor physical function, and cognitive deficits—that resemble conditions in the elderly. Standard HIV treatment suppresses the virus but does not prevent these ageing-like complications. The researchers hypothesise that HIV acquired at birth accelerates the fundamental biological processes of ageing, driving long-term health decline. Current knowledge cannot explain why this happens or how to stop it. Over 24 months, the team will follow 800 children aged 6–9 in Harare—400 with HIV on therapy and 400 HIV-negative peers. They will measure growth, physical and cognitive function, and analyse specific hallmarks of biological ageing in blood samples. The goal is to identify which ageing mechanisms drive the deficits and which factors might protect against them. If successful, this work could reveal targets for future treatments that slow or prevent ageing-related damage in children with HIV. It may also deepen fundamental understanding of how biological ageing works in young bodies, with potential relevance to ageing research more broadly.

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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.

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Researchers

Barbara Kronsteiner-Dobramysl (EPMC Awardee)Celia Gregson (EPMC Awardee)Hannah Elliott (EPMC Awardee)Laura Howe (EPMC Awardee)Nyasha Dzavakwa (EPMC Awardee)Rashida Ferrand (EPMC Awardee)Tafadzwa Madanhire (EPMC Awardee)Thomas Jackson (EPMC Awardee)Tsitsi Bandason (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

The molecular basis of ageing in HIV infection.
Cognitive function in HIV-exposed uninfected children in rural Zimbabwe
The Causes and Consequences of Residual Immune Activation in HIV-infected Children on ART in Resource-Limited Settings
ImpRoving outcomEs of inFants, chIldreN, and adolEscents with HIV (REFINE)
NIHR Global Health Professorship in Healthy Ageing in Sub-Saharan Africa

Original classification

Discovery Award

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