Development and Internal Validation of a Two-Year Prognostic Risk Index for Functional Decline in Adults Aging with HIV

INTRODUCTION: People with HIV (PWH) are at risk for functional decline and disability due to a complex interplay of factors, yet longitudinal studies of everyday functioning in this population are lacking. To identify individuals at risk for functional decline, we developed an internally validated, point-based prognostic risk index. METHODS: 742 PWH were assessed in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study at five visits over two years. To select predictors of self-reported functional dependence, a binary logistic regression was performed using Akaike information criterion-guided backward stepwise selection. Model performance, discrimination, and calibration were assessed. The final model was internally validated by bootstrapping and optimism corrected. Risk index scores were generated using adjusted beta coefficients and a risk score cut-off was determined. RESULTS: Baseline predictors of functional dependence included elevated depressive symptoms, thrombocytopenia (platelets <150x103/μL), fine motor skills impairment, older age, and unemployment. White race, chronic pulmonary disease, and lifetime major depressive disorder were also retained. The risk score ranged from 0-63 points with a threshold value having good sensitivity (81%) and discriminability (c-statistic = 0.80) for functional dependence. However, it also had only moderate specificity (70%) with a high false positive rate. CONCLUSIONS: A combination of demographics, fine motor skills, depression, and medical conditions predict functional decline. Additional studies examining external validity of the index in large, age-diverse samples of PWH with functional impairment are required before deployment in clinical settings.