Higher Anti-Cytomegalovirus Immunoglobulin G Concentrations Are Associated With Worse Neurocognitive Performance During Suppressive Antiretroviral Therapy

Abstract

Background: Cytomegalovirus (CMV) has been linked to higher risk of cardiovascular disease and mortality. We aimed to determine if CMV is associated with neurocognitive performance in adults infected with human immunodeficiency virus (HIV).

Methods: In this cross-sectional analysis, anti-CMV immunoglobulin G (IgG) concentrations in blood and CMV DNA copies in blood and cerebrospinal fluid (CSF) were measured in stored specimens of 80 HIV-infected adults who were previously assessed with a comprehensive neurocognitive test battery. Thirty-eight were taking suppressive antiretroviral therapy (ART) and 42 were not taking ART. A panel of 7 soluble biomarkers was measured by immunoassay in CSF.

Results: Anti-CMV IgG concentrations ranged from 5.2 to 46.1 IU/mL. CMV DNA was detected in 7 (8.8%) plasma specimens but in no CSF specimens. Higher anti-CMV IgG levels were associated with older age (P = .0017), lower nadir CD4+ T-cell count (P < .001), AIDS (P < .001), and higher soluble CD163 (P = .009). Higher anti-CMV IgG levels trended toward an association with worse neurocognitive performance overall (P = .059). This correlation was only present in those taking suppressive ART (P = .0049). Worse neurocognitive performance remained associated with higher anti-CMV IgG levels after accounting for other covariates in multivariate models (model P = .0038). Detectable plasma CMV DNA was associated with AIDS (P = .05) but not with neurocognitive performance.

Conclusions: CMV may influence neurocognitive performance in HIV-infected adults taking suppressive ART. Future clinical trials of anti-CMV therapy should help to determine whether the observed relationships are causal.

Figure 1.

Correlates of anti–cytomegalovirus (CMV) immunoglobulin G (IgG). Higher anti-CMV IgG concentrations in serum correlated with older age (A), lower nadir CD4⁺ T-cell counts (B), and AIDS (C). “+” indicates the subgroup mean.

Figure 2.

Associations between anti–cytomegalovirus (CMV) immunoglobulin G (IgG) levels and neurocognitive functioning. A, Higher anti-CMV IgG concentrations in serum correlated with worse global T scores in participants who were taking suppressive antiretroviral therapy (ART). The P value for the interaction between anti-CMV IgG and ART use in predicting global T score was .045. B, During suppressive ART, higher anti-CMV IgG levels were associated with neurocognitive impairment (NCI).

Figure 3.

Higher anti–cytomegalovirus (CMV) immunoglobulin G (IgG) levels in serum correlated with cerebrospinal fluid (CSF) biomarkers in subgroups. A, Higher anti-CMV IgG in serum correlated with higher soluble CD163 in CSF in participants taking suppressive antiretroviral therapy (ART). B, Higher anti-CMV IgG in serum correlated with higher human immunodeficiency virus (HIV) RNA levels in CSF in participants not taking ART.