Short Communication: Do Cytomegalovirus Antibody Levels Associate with Age-Related Syndromes in HIV Patients Stable on Antiretroviral Therapy?

Abstract

HIV(+) persons stable on antiretroviral therapy (ART) face early onset of age-related diseases. This may arise from a high burden of cytomegalovirus (CMV). To address the role of CMV, we investigated univariate and multivariate associations between markers of systemic and endothelial inflammation, vascular damage, insulin resistance (IR), neurocognitive decline, and antibodies reactive with CMV. In this study, HIV(+) participants (n = 91) aged >45 years with <50 copies HIV RNA/ml plasma after >2 years on ART were assessed for cardiovascular risk (the D:A:D algorithm), type II diabetes (the HOMA-IR index), and neurocognitive performance. Blood samples were assayed for lipids, T cells, insulin, glucose, C-reactive protein, CX3CL1, sTNF-R1, total immunoglobulin G (IgG), and antibodies reactive with CMV lysate, glycoprotein B, or immediate-early-1. Levels of antibodies detected with the three antigens were tightly correlated. Levels of CMV lysate antibody were higher in patients than in age-matched healthy controls and reflected their nadir CD4 T-cell count (p = .001), total IgG (p = .02), and age (p = .08). Levels of CMV lysate antibody correlated with D:A:D score (p = .04), neurocognitive performance (p = .045), and fasting insulin (p = .02). In multivariable analyses, some associations reflected the effect of age, but CMV lysate antibody and CD8 T-cell counts were significant predictors of the HOMA-IR index (R(2) = 0.09, p = .01) independent of age. We conclude that associations between levels of CMV antibodies, cardiovascular risk, and neurocognitive health in HIV(+) patients stable on ART are moderated by age-associated increases in response to CMV, while CMV antibodies may be independently linked with IR.

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.…”

“…Since we had limited knowledge of other co-infections, and did not measure B-cell activation markers or total IgG levels, we cannot exclude the potential for residual confounding, particularly due to aberrant B-cell activation. Notably, however, a previous study demonstrated increases in CMV-specific IgG antibody levels during HIV disease progression that were not seen for IgG levels specific to other co-infections [49] , and weak correlations have been observed between total IgG levels and CMV lysate antibody levels among HIV-infected individuals on ART [12] . It should also be noted that the results from this study may not be generalizable to men or resource-rich settings.…”

“…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] .…”

Cytomegalovirus and HIV: A Dangerous Pas de Deux

“…In addition, the combination of higher serum anti-CMV IgG titers and higher plasma levels of the monocyte activation biomarker, soluble CD163, were strongly associated with global neurocognitive impairment (odds ratio, 5.7; positive predictive value, 83%). Another recent study of 91 HIV-infected adults taking suppressive ART found a consistent association between higher anti-CMV IgG levels and worse neurocognitive performance, although this weakened when age was included in the model [111].…”

Metabolic Complications and Glucose Metabolism in HIV Infection: A Review of the Evidence

“…[69] A recent investigation also identified an association of cytomegalovirus (CMV) infection with insulin resistance; duet to the high burden of CMV in older PLWH this represents a potential mechanism to treat altered glucose metabolism in that group. [70] Additionally, interventions designed to decrease chronic inflammation could potentially improve metabolic function in people aging with HIV.…”