Background
The associations among inflammatory markers and prevalent or incident frailty, cognitive impairment (CI), clinical events and all-cause mortality in older people with HIV are poorly understood.
Methods
Participants from the HAILO study ≥50 years were included. Frailty was evaluated using the Fried Frailty assessment (4-meter walk speed, grip strength, unintentional weight loss, exhaustion, low activity) and CI with the Neuroscreen (Trail Making A, Trail Making B, and Digit Symbol and Hopkins Verbal Learning Test). Included clinical events combined non-AIDS defining cancers, diabetes and cardiovascular, liver and kidney diseases. Baseline inflammatory markers included hsCRP, TNFR1, IL-6, CXCL-9 and inflammatory index score (1/3log(IL-6)+2/3 log(TNFR1)). Multivariable logistic regression and Poisson regression were used to examine associations among inflammatory markers and prevalence and incidence of frailty, CI, clinical events and all-cause mortality. Lastly, we used 10-fold cross validation to examine whether addition of inflammatory markers to frailty improve ability to predict incident clinical events.
Results
Among 484 participants included (17% assigned female at birth, 25% Black and 20% Hispanic), median age was 56 years. Median BMI was 27 kg/m2, median CD4 and nadir CD4 were 627 and 189 cells/µL, and 95% had HIV RNA <200 copies/mL. 8% (38/484), 32% (144/453) and 43% (210/484) participants had frailty, CI and major clinical events at baseline. IL-6, TNFR1, CXCL-9 and inflammatory index score were associated with increased risk of prevalent frailty and clinical events, but not CI, at baseline (Figure). Incident rates (95%CI) of frailty, CI and clinical events were 3.72 (2.93-4.64), 9.58 (7.93-11.49) and 6.28 (5.02-7.75) per 100 person-years, respectively. CXCL-9 (Q4 vs. Q1) and TNFR1 were associated with an increased risk of incidence of both frailty and clinical events; inflammatory index was associated with only clinical events in the quartile analysis (Q4 vs. Q1), and higher inflammatory markers included (except CXCL-9) were also associated with an increased risk of all-cause mortality. The addition of TNFR1 or inflammatory index to baseline frailty increased the predictability of incident clinical events and mortality.
Conclusions
Increased inflammation was associated with increased risk of prevalent and incident frailty and major clinical events/all-cause mortality, but not CI. Inflammatory markers and frailty together may better predict clinical events and mortality.