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. 2015 Sep;31(9):905-12.
doi: 10.1089/AID.2015.0085. Epub 2015 Jul 8.

Physical function impairment of older, HIV-infected adults is associated with cytomegalovirus immunoglobulin response

Kristine M Erlandson  1 , Amanda A Allshouse  2 , Eric Rapaport  1 , Brent E Palmer  1 , Cara C Wilson  1 , Adriana Weinberg  1   3   4 , Samantha MaWhinney  2 , Thomas B Campbell  1
Affiliations

Physical function impairment of older, HIV-infected adults is associated with cytomegalovirus immunoglobulin response

Kristine M Erlandson et al. AIDS Res Hum Retroviruses. 2015 Sep.

Abstract

Cytomegalovirus (CMV) is associated with poor outcomes, including physical function impairment, in older HIV-uninfected adults. Whether CMV is associated with physical functional impairment in HIV-infected adults is unknown. The primary objective of this study was to determine the relationship between CMV-specific humoral and cell-mediated immune responses with functional impairment in well-controlled HIV infection. In a case-control study, low-function cases were matched by age, gender, and time from HIV diagnosis to high-function controls. Quantitative CMV IgG and %CMV-specific CD8(+) and CD4(+) T cells (interferon-γ expression following CMV pp65 stimulation) were used to estimate physical function. Among 30 low-function cases and 48 high-function matched controls, CMV IgG ranged from <10 to 8,830 EU/ml, including four controls with results <10 EU/ml. Each log10 increase in CMV IgG was associated with 5-fold greater odds of low function (p=0.01); these findings were robust to adjustment for concomitant CD4(+) count, tobacco use, and age; to exclusion of subjects with CMV IgG <10 EU/ml; and to adjustment for hepatitis C viremia. %CMV-specific CD4(+) or CD8(+) T cells were not associated with low function. In bivariable models, the relationship between CMV IgG and physical function was attenuated and was no longer significant when including IL-6, CD4/CD8 ratio, or the Veterans Aging Cohort Study Index score. High levels of CMV-specific IgG were associated with impaired physical function. Attenuation of the strength of this association in bivariable models suggests an indirect relationship mediated by systemic inflammation and immune suppression.

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Figures

<b>FIG. 1.</b>
FIG. 1.
Distribution of cytomegalovirus IgG (A), herpes simplex virus 1 and 2 IgG (B), varicella zoster virus IgG (C), % CMV-specific CD4+ T cells (D), and % CMV-specific CD8+ T cells (E) between low and high physical function groups. Group geometric means are indicated by the solid line. The assay limits of detection for the immunoglobulin assays are indicated by the dotted line, with the exception of varicella zoster virus where all participants were positive.
<b>FIG. 2.</b>
FIG. 2.
Correlations between cytomegalovirus (CMV) humoral or cell-mediated immune response and baseline characteristics, inflammation, activation, and senescence markers. (A–C) Correlations including all subjects (diamond) are shown in the left panels; correlations separated by high (square) and low (circle) physical function are shown in the right panels.
<b>FIG. 3.</b>
FIG. 3.
(A) The odds of having low physical function by each variable listed on the y-axis (univariable models). The dot indicates the increase in the odds of low function per 1 unit increase in CMV IgG and the CD4/CD8 ratio per 0.2 pg/ml increase in interleukin (IL)-6, per 10% increase in %CD8CD38HLA-DR, per 10 point increase in the VACS Index score, per 5 year increase in age, and per 100 cells/μl increase in CD4+ count. The dotted line marks an odds ratio of 1. (B) The odds of low physical function per 1 unit increase in CMV IgG, with each bivariable model including CMV and the single corresponding variable. The dotted line marks an odds ratio of 1 and the dashed line marks the unadjusted odds of low function per increase in CMV IgG, for visual comparison.
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