Association of Functional Impairment with Inflammation and Immune Activation in HIV Type 1–Infected Adults Receiving Effective Antiretroviral Therapy

A cornerstone of successful aging is the ability to maintain functional independence [1, 2]. A key and often modifiable element of functional independence is the preservation of physical function. Physical function impairments in older adults increase the risk of morbidity and mortality. Among aging individuals without human immunodeficiency virus type 1 (HIV-1) infection, declines in physical function and development of frailty are strongly associated with inflammation and immune system dysfunction, including immune activation, immunosenescence, and altered levels of T-lymphocyte subsets [3–8]. Aging with HIV infection is associated with early decline in physical function and development of frailty [9]. Early development of frailty or a frailty-like syndrome has been demonstrated in several HIV cohorts, although findings have been most apparent in those who are not receiving antiretroviral therapy or have the lowest CD4+ T-cell counts [10–14]. Performance-based measures targeted at the upper end of the functional spectrum among middle-aged and older adults with HIV infection have identified greater than expected impairments in walking speed, balance, ability to rise from a chair, and peak exercise capacity [15, 16]. Given that immune activation and inflammation have been associated with impaired physical function and frailty in older non–HIV-infected persons and because HIV infection is associated with chronic immune activation and inflammation despite otherwise successful antiretroviral therapy [17], we hypothesized that functional impairment during HIV infection is associated with markers of immune activation and inflammation. Because immunosenescence is associated with frailty in non–HIV-infected elderly patients and because immunosenescence and microbial translocation have been associated with chronic HIV infection, we further hypothesized that markers of immunosenescence and microbial translocation would also be associated with functional impairment.