LAUSR

OBJECTIVE Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes in HIV-infected and uninfected adults. Frailty is a dynamic state, yet little data exist on predictors and consequences of frailty transitions. DESIGN/METHODS Frailty was assessed semiannually among HIV-infected and uninfected persons with prior injection drug use (PWID) using the 5 Fried phenotype domains. An inflammatory index score (IIs) was constructed from interleukin-6 and soluble tumor necrosis factor-α receptor-1 data. Markov transition models assessed determinants of frailty transitions. Cox proportional hazards models estimated mortality risk. RESULTS Among 1353 ALIVE participants with 9559 frailty transition assessments, 33% were HIV-infected. Younger age, higher education, employment, reduced comorbidity, HIV virologic suppression, elevated CD4 nadir (>500) and absence of a prior AIDS diagnosis were significantly associated with both reduced frailty progression and greater frailty recovery. Each standard deviation decrease in IIs was associated with decreased frailty progression (OR 0.78; 95% CI, 0.65, 0.92) and increased frailty recovery (OR 1.29; 95% CI, 1.08, 1.53). Being frail at 1 of 2 consecutive visits was associated with increased mortality, compared to maintenance of a nonfrail state. Being frail at both of 2 consecutive visits demonstrated the highest mortality risk (HR 3.23; 95% CI, 2.1, 4.96). CONCLUSIONS Sustained, and to a lesser degree, intermittent frail states are associated with increased mortality. HIV virologic suppression with earlier ART, reduced comorbidity, and reduced inflammation may prevent frailty progression and promote frailty recovery, consequently improving survival for persons aging with HIV and PWID.