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J Infect Dis. 2013 Jul 15;208(2):249-59. doi: 10.1093/infdis/jit147. Epub 2013 Apr 4.

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

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Division of Infectious Diseases, University of Colorado, Denver, USA.



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.


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.


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.


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.


HIV; aging; frailty; functional capacity; functional impairment; functional status; immune activation; immunosenescence; inflammation; microbial translocation; physical function; senescence; telomeres

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