Anticholinergic burden interacts with age and AIDS history to amplify frailty in people with HIV

Background: In ageing people with human immunodeficiency virus (HIV), frailty, multimorbidity and polypharmacy are prevalent. Anticholinergic medications are commonly prescribed in this population and are associated with adverse physical and cognitive outcomes, yet their contribution to frailty phenotypes remains insufficiently characterized. Methods: We conducted a cross-sectional study of people with HIV receiving care at a tertiary HIV clinic in Northern Italy. Anticholinergic burden (ACB) was quantified using the Anticholinergic Cognitive Burden scale. Frailty was assessed using the modified Fried phenotype and the deficit-accumulation Rockwood index. Multivariable linear models with interaction terms (IT) and perturbation analyses were used to evaluate independent associations between ACB and frailty scores and to assess effect modification by demographics and clinical factors. Results: A total of 1200 participants were included (mean age of 52 ± 12 years; 95.5% with HIV-RNA < 50 copies/mL; 19.0% receiving anticholinergic medications). By Fried criteria, 38.7% were pre-frail and 6.9% frail, with Rockwood score increasing stepwise across these groups. ACB was among the strongest independent correlates of frailty (Fried: aβ 0.32 [0.25-0.40], p < .001; Rockwood: aβ 0.69 [0.61-0.77], p < .001), alongside age and chronic kidney disease. With the Fried phenotype, the impact of ACB significantly intensified with age (IT aβ 1.17, p < .001), prior acquired immunodeficiency syndrome (AIDS) (IT aβ 0.35, p < .001) events and longer HIV duration (IT aβ 0.16, p = .023). Conclusions: ACB is a modifiable contributor to frailty in people with HIV, with disproportionate impact on older individuals and those with prior severe immunosuppression. Incorporating routine ACB assessment and deprescribing strategies into HIV care may help support functional ageing and reduce vulnerability.