Increased inflammation but similar physical composition and function in older-aged, HIV-1 infected subjects

Abstract

Background: Systemic immune activation (inflammation) and immunosenescence develop in some people with advancing age. This process, known as "inflamm-aging," is associated with physical frailty and sarcopenia. Meanwhile, successful antiretroviral therapy has led to a growing number of older HIV-1-infected individuals who face both age-related and HIV-1-related inflammation, which may synergistically promote physical decline, including frailty and sarcopenia. The purpose of our study was to determine if inflammation during treated HIV-1 infection worsens physical impairment in older individuals.

Methods: We determined the severity of HIV-associated inflammation and physical performance (strength and endurance) in 21 older HIV-infected individuals (54-69 years) receiving suppressive antiretroviral therapy, balanced for confounding variables including age, anthropometrics, and co-morbidities with 10 uninfected control individuals. Biomarkers for microbial translocation (lipopolysaccharide [LPS]), inflammation (soluble CD14 [sCD14], osteopontin, C-reactive protein [CRP], interleukin-6 [IL-6], soluble ICAM-1 [sICAM-1] and soluble VCAM-1 [sVCAM-1]), and coagulopathy (D-dimer) were assayed in plasma. Activation phenotypes of CD4(+)T cells, CD8(+) T cells and monocytes were measured by flow cytometry. Physical performance was measured by 400 m walking speed, a short physical performance battery [SPPB], and lower extremity muscle strength and fatigue.

Results: Overall physical function was similar in the uninfected and HIV-infected groups. Compared to uninfected individuals, the HIV-infected group had elevated levels of sCD14 (P < 0.001), CRP (P < 0.001) and IL-6 (P = 0.003) and an increased frequency of CD4(+) and CD8(+) T cells with an immunosenescent CD57(+) phenotype (P = 0.004 and P = 0.043, respectively). Neither plasma inflammatory biomarkers nor CD57(+) T cells correlated with CD4(+) T cell counts. Furthermore, none of the elevated inflammatory biomarkers in the HIV-infected subjects were associated with any of the physical performance results.

Conclusions: When age-related co-morbidities were carefully balanced between the uninfected and HIV-infected groups, no evidence of inflammation-associated physical impairment was detected. Despite careful balancing for age, BMI, medications and co-morbidities, the HIV-infected group still displayed evidence of significant chronic inflammation, including elevated sCD14, CRP, IL-6 and CD57(+) T cells, although the magnitude of this inflammation was unrelated to physical impairment.

Fig. 1

Reduced frequency of monocytes among PBMCs from HIV-infected subjects. a PBMC samples were analyzed by flow cytometry by first gating on the total mononuclear cells and then measuring the frequency of CD14⁺ cells for each individual (representative subjects). b The frequency of CD14⁺ monocytes among PBMCs from 21 HIV-infected subjects was compared to that of 10 uninfected controls using unpaired t-tests. c Using flow cytometry, the mean fluorescence intensity for a panel of monocyte maturation/activation markers was determined for CD14⁺ cells. No differences were found between the groups

Fig. 2

Increased frequency of CD57-expressing CD4⁺ and CD8⁺ T cells in HIV-infected subjects. PBMC samples were analyzed by flow cytometry by first gating on the total mononuclear cells and then on the CD3⁺ T cells. The frequency of CD57⁺ cells among the (a) total CD4⁺ T cells, (b) CD28-expressing CD4⁺ T cells or (c) CD28-negative CD4⁺ T cells was determined. Next, the frequency of CD57⁺ cells among the (d) total CD8⁺ T cells, (e) CD28-expressing CD8⁺ T cells or (f) CD28-negative CD8⁺ T cells was determined using Mann–Whitney U-tests. The error bars represent ± 1 SD

Fig. 3

Frequency of CD45RO-expressing memory CD4⁺ T cells, but not CD57⁺ CD4⁺ T cells, is associated with CD4⁺ T cell decline. PBMC samples were analyzed by flow cytometry by first gating on the total mononuclear cells and then on the CD3⁺ T cells. The frequency of (a) CD4⁺ CD45RO⁺ T cells was then determined. The correlations between total peripheral blood CD4⁺ T cell counts and (b) T cells CD4⁺ CD45RO⁺ T cells, (c) CD4⁺ CD28⁺ CD57⁺ T cells, or (d) CD8⁺ CD28⁻ CD57⁺ T cells were determined (Pearson correlation)