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Frailty and All-Cause Mortality among People with HIV Engaged in Clinical Care in the United States
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JAIDS Dec 2025
Early identification of frailty symptoms and interventions, such as exercise training, to minimize and mitigate frailty progression, are crucially important in prioritizing healthy aging among PWH and reducing mortality.
Most evidence points to exercise and physical activity as potent priorities for frailty intervention.34,37 In particular, activity regimens that integrate multiple components of exercise (e.g., cardiovascular, resistance training and balance/flexibility exercise) and significant repetition for several months had positive impact on several frailty components.34,38
Abstract
Background:
Frailty occurs at younger ages among people with HIV (PWH) than those without HIV, but its impact on mortality is unknown.
Methods:
We examined the association between frailty (defined by a validated phenotype including inactivity, fatigue, weight loss, and immobility) and mortality (ascertained from state and national death data) among PWH in the CFAR Network of Integrated Clinical Systems (CNICS) cohort between 1/2015-3/2024 using adjusted Cox proportional hazards models.
Results:
Among 6,750 PWH in this study, average age was 50 years, 15% were female, 44% were prefrail, 11% were frail at baseline, and the incidence of frailty was 9.7 per 1000 person-years (95% Confidence Interval [CI]:8.8-10.8) over an average of 5.5 years of follow-up. In adjusted models, frailty was associated with 2.7-times (95%CI:2.0-3.6), and prefrailty with 1.5-times (95%CI:1.2-2.0), higher risk of mortality. Prefrailty and frailty were consistently associated with an increased risk of death in models stratified by age (<50 vs. ≥50) and sex (male vs. female). Frailty was associated with 3.6-times (95%CI:2.2-6.1) and 2.5-times (95%CI:1.7-3.5) higher risk of mortality among PWH <50 and ≥50, respectively, and with 2.6-times (95%CI:1.9-3.6) and 3.9-times (95%CI:1.7-8.9) higher risk among male and female PWH, respectively.
Conclusions:
In a large cohort of PWH, frailty and prefrailty were associated with a greater risk of death among PWH of all ages. Preventing frailty in this high-risk population is an important public health priority.
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