Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy

Abstract

Background. The relationships of inflammation, immune activation, and immunosenescence markers with functional impairment in aging human immunodeficiency virus type 1 (HIV-1)-infected persons are unknown.Methods. HIV-infected persons who were aged 45-65 years, had a plasma HIV-1 RNA load of <48 copies/mL, and were receiving antiretroviral therapy underwent standardized functional testing. In a nested case-control analysis, low-functioning cases were matched (1:1-2) by age, sex, and HIV-1 diagnosis date to high-functioning controls. Markers of inflammation, T-cell activation, microbial translocation, immunosenescence, and immune recovery were used to estimate functional status in conditional logistic regression. Primary analyses were adjusted for CD4+ T-cell count, smoking, and hepatitis.Results. Thirty-one low-functioning cases were compared to 49 high-functioning controls. After statistical adjustment, lower proportions of CD4+ T cells and higher proportion of CD8+ T cells, higher CD38/HLA-DR expression on CD8+ T cells, and higher interleukin-6 were associated with a significantly greater odds of low functional status (odds ratio, ≥ 1.1 for all analyses; P ≤. 03). Other inflammatory, senescence, and microbial translocation markers were not significantly different (P ≥. 11 for all analyses) between low-functioning and high-functioning groups.Conclusions. Functional impairment during successful antiretroviral therapy was associated with higher CD8+ T-cell activation and interleukin 6 levels. Interventions to decrease immune activation and inflammation should be evaluated for their effects on physical function and frailty. © 2013 The Author 2013. All rights reserved.