Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 208, Issue 2, Pages 249-259Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit147
Keywords
HIV; functional capacity; functional status; inflammation; immune activation; aging; immunosenescence; telomeres; physical function; functional impairment; frailty; microbial translocation; senescence
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Funding
- National Institutes of Health [5ULTR000154, R03AG040594-01, T32 AI007447-1]
- Hartford Foundation Center of Excellence in Geriatric Medicine
- GlaxoSmithKline (HIV Collaborative Investigator Research Award)
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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.
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