Growing Old and Frail with HIV

This thesis investigates the health consequences of ageing in people with HIV compared to people without HIV using data from the longitudinal AGEₕIV Cohort Study. Although effective antiretroviral therapy has transformed HIV into a manageable chronic condition, earlier cross-sectional studies had shown people with HIV to be more likely to experience age-associated comorbidities and frailty.
The research described in this thesis extends these findings and shows that over time people with HIV continue to have a higher mean number of comorbidities than people without HIV. While the rate of comorbidity increase is similar across both groups as they age, people with HIV consistently experience a higher burden of diseases. The higher burden in people with HIV is linked to more years of life lost, primarily due to non-AIDS malignancies. Furthermore, frailty was found to be a robust independent predictor of both mortality and new-onset comorbidities in middle-aged populations, regardless of HIV status. However, people with HIV experience a significantly higher prevalence of frailty. The increased risk of people with HIV transitioning to frailty is mainly associated with a higher waist–hip ratio, a greater burden of existing comorbidities, and the presence of depressive symptoms.
Additionally, one of the included studies demonstrates that people with HIV exhibit a distinct gut microbiota signature that is independent of sex or sexual practices. This signature correlates with systemic inflammation markers, particularly suPAR (soluble urokinase plasminogen activator receptor), and a higher prevalence of age-associated comorbidities.
These findings highlight the urgent need for a multidisciplinary care model that integrates geriatric principles into HIV medicine. Recommendations include routine frailty assessments, proactive falls prevention, regular medication reviews, and optimised screening for non-AIDS malignancies to ensure a good quality of life for the ageing population of people with HIV.