Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

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 highfunction controls. Quantitative CMV IgG and %CMV-specific CD8 + and CD4 + T cells (interferon-c 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 log 10 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.

Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

“…Similarly, among women on ART for a median of 4-5 months, we noted that elevated post-ART CMV IgG antibody levels were associated with higher plasma immune activation markers. There is considerable variability between studies in precisely which immune activation markers are associated with post-ART CMV IgG levels [11, 13, 26, 44-47] , but our findings are consistent with the model suggesting that CMV has a role in driving persistent immune activation during suppressive ART [25] . The durability of these associations require confirmation during long-term ART use.…”

“…The humoral immune response to CMV, as measured by CMV-specific immunoglobulin G (IgG) antibody, has also been linked to untreated HIV disease progression in men who have sex with men (MSM) [8, 9] . Despite use of antiretroviral therapy (ART), CMV co-infection is associated with increased risk of poor non-AIDS related events [10] , and high CMV IgG antibody levels are associated with subclinical cardiovascular disease [11] , impaired neurocognitive function [12] , and decreased physical function [13] . Interestingly, similar findings have also been made among general populations in the U.S. and Europe [14-17] .…”

“…Numerous investigations have suggested that CMV replication continues to drive CD8 + T-cell expansion and inflammation in ART-experienced individuals [20-25] . The cross-sectional evidence is conflicting in untreated and treated HIV-infected individuals, but some studies suggest CMV IgG antibody levels may also be associated with immune activation markers, such as C-reactive protein (CRP) [13] , a general biomarker of systemic inflammation, and soluble CD14 (sCD14) [26] ,a biomarker of nonspecific monocyte activation [27] .…”

Basic Principles of Nutrition, HIV and AIDS: Making Improvements in Diet to Enhance Health

“…However, inadequate food intake, due to a variety of etiologies, malabsorption and altered metabolism, may also contribute to malnutrition. Additionally, factors in food, including reduced micronutrient levels, can negatively affect the immune functions and result in increase in the progression of HIV infection at all stages [8][9][10][11].…”

HIV and aging: time to bridge the gap between clinical research and clinical care

“…In this one, the authors underline the core that constitutes the geriatrician's specific expertise and suggest putting it toward the service of complex older adults with HIV to bring value with the development of CGA integrated in a multidisciplinary team led by HIV specialists. As they point out, most older adults with HIV nowadays are robust and do not need a geriatrician's intervention, but one in four suffer from geriatric syndromes and, specifically, functional impairment [7,[11][12][13], and this 25% will be surely benefit from a geriatrician's evaluation through the CGA.…”