Abstract
Concomitant with the prolonging of lifespan for persons living with HIV (PLWH) is the management of geriatric syndromes such as frailty. This is due to its ability to predict functional impairment and mortality among older adults. Frailty onset occurs earlier and at higher rates in PLWH than in the general population. Numerous predictors of frailty have been identified, spanning several domains. Frailty presents in PLWH as a multi-system syndrome with evidence of dysregulation across biological, immune, neural, cognitive, and psychosocial domains. However, it is unclear which domains are germane to frailty status in older adult PLWH. The present study used stochastic search variable selection (SSVS) to identify the most reliable predictors of the frailty phenotype in a sample of 44 middle-aged and older PLWH (M age = 62.27 years) from a set of 111 multimodal predictors. While none of these predictors exceeded the conventional threshold for marginal inclusion probabilities (MIP > 0.5), several variables emerged with MIPs above 0.25. Lower mean diffusivity of the cingulum, greater resting state connectivity of the posterior salience network, reduced brain volume, higher LF:HF ratio, slower psychomotor speed, and greater basal ganglia activation during a forced grip generation task were relatively strong predictors of frailty. This pattern of predictors implies a structural deficit that likely contributes to slowed information processing, compensatory striatal activity during physical exertion, and a state of neurovisceral exhaustion evidenced by sympathetic overdrive, depressed state, and network connectivity indicative of hyper-focus on internal states.