Immune Activation in HIV-Infected Aging Women on Antiretrovirals—Implications for Age-Associated Comorbidities: A Cross-Sectional Pilot Study

Abstract

BackgroundPersistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages.MethodsTwenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163), microbial translocation (LPS) and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10) were evaluated.ResultsT cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation.ConclusionsHIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls.

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

“…[22][23][24] Increased immune activation of monocytes was reported to be involved in HIV-1 pathogenesis and thus associated with CVD risk. 17,28,29 In the present study, we demonstrated that in contrast to the decreased percentage of CD14 high CD16 2 monocyte subset, CD14 dim CD16 1 and CD14 high CD16 1 monocyte subsets were expanded during both primary and chronic HIV-1 infection. This was the first report of the monocyte subset distribution in primary HIV-1 infection, and it expanded previous observations that had focused on chronic HIV-1-infected patients, HARRT patients, and elite controllers.…”

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

“…One of these markers, soluble CD25, is a general marker of IA and is elevated in diabetes, autoimmune disease, cancer, and immunodeficiency diseases (46). We previously showed that plasma sCD25 is elevated in HIV + compared with HC postmenopausal women (47). Although sCD25 showed a positive correlation with age in HC, it was selected as a significant negative predictor of vaccine response in the HIV + group only.…”

Review of Cardiovascular Disease in HIV-Infected Women

“…Conceivably, HIVinfected patients may have higher rates and increased risk of CHD because of increased levels of inflammation and immune activation than seronegative patients. This increased immune activation persists even in patients on ART who have achieved virological suppression and immune reconstitution with CD4 cell count >200 mm 3 [33]. Soluble CD163 (sCD163) is a monocyte-macrophage specific scavenger receptor cleaved from activated monocytes and macrophages during inflammation, and elevated levels have been associated with coronary artery disease in the general population and HIV-infected men suggesting this inflammatory and immune pathway may be involved in the pathogenesis of atherosclerosis [34,35].…”