Objectives: Associations between inflammatory markers and prevalent or incident frailty, cognitive impairment, clinical events, and mortality in older people with HIV are poorly understood. Design: An observational cohort study. Methods: Participants aged at least 50 years from the ACTG HAILO cohort study were included. Participants completed annual evaluations for cognitive impairment and frailty. Clinical events included non-AIDS-defining cancers, diabetes, and cardiovascular, liver, and kidney diseases. Associations between inflammatory markers (hsCRP, IL-6, TNFR1, CXCL-9, and inflammatory index score [IIS]) at baseline and prevalence and incidence of frailty, cognitive impairment, any clinical event, and non-accidental mortality were examined. We used 10-fold cross validation to evaluate whether the combination of inflammatory markers and frailty improved the ability to predict incident outcomes. Results: Among 484 participants (17% assigned female at birth, 25% Black, and 20% Hispanic), median age was 56 years. Median BMI was 27 kg/m2 , median CD4+ cell count was 627 cells/l, and 95% had HIV-1 RNA less than 200 copies/ml. HsCRP, IL-6, TNFR1, CXCL-9, and IIS were associated with increased risk of prevalent frailty and clinical events, but not cognitive impairment. CXCL-9 (Q4 vs. Q1) and TNFR1 were associated with an increased incidence of both frailty and clinical events; Q4 vs. Q1 of the IIS was associated with clinical events; increased inflammatory markers (except CXCL-9) were associated with an increased risk of mortality. TNFR1 combined with frailty modestly improved the predictability of incident clinical events and mortality over frailty alone.

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