Inflammatory and immune markers in HIV‐infected older adults on long‐term antiretroviral therapy: Persistent elevation of sCD14 and of proinflammatory effector memory T cells. Issue 9 (16th August 2022)

• Record Type: Journal Article
• Authors: Watanabe, Makiko; Jergovic, Mladen; Davidson, Lisa; LaFleur, Bonnie J.; Castaneda, Yvonne; Martinez, Carmine; Smithey, Megan J.; Stowe, Raymond P.; Haddad, Elias K.; Nikolich‐Žugich, Janko
• Is Part Of: Aging cell. Volume 21:Issue 9(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-16
• Subjects: antiretroviral therapy -- HIV -- immune aging -- sCD14; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13681
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: HIV‐positive patients whose viral loads are successfully controlled by active antiretroviral therapy (ART) show no clinical signs of AIDS. However, their lifespan is shorter compared with individuals with no HIV infection and they prematurely exhibit a multitude of chronic diseases typically associated with advanced age. It was hypothesized that immune system aging may correlate with, and provide useful biomarkers for, this premature loss of healthspan in HIV‐positive subjects. Here, we tested whether the immune correlates of aging, including cell numbers and phenotypes, inflammatory status, and control of human cytomegalovirus (hCMV) in HIV‐positive subjects on long‐term successful ART (HIV+) may reveal increased "immunological age" compared with HIV‐negative, age‐matched cohort (HIV−) in participants between 50 and 69 years of age. Specifically, we expected that younger HIV+ subjects may immunologically resemble older individuals without HIV. We found no evidence to support this hypothesis. While T cells from HIV+ participants displayed differential expression in several differentiation and/or inhibitory/exhaustion markers in different T cell subpopulations, aging by a decade did not pronounce these changes. Similarly, while the HIV+ participants exhibited higher T cell responses and elevated inflammatory marker levels in plasma, indicative of chronic inflammation, this trait was not age‐sensitive. We did find differences in immune control of hCMV, and, more importantly, a sustained elevation of sCD14 and of proinflammatory CD4 and CD8 T cell responses across age groups, pointing towards uncontrolled inflammation as a factor in reduced healthspan in successfully treated older HIV+ patients. Abstract : Proinflammatory markers, such as sCD14, in plasma and proinflammatory responses of T cells were elevated in successfully treated HIV+ compared with HIV− older adults age‐independently. The higher number of naïve CD8 T cells, higher expression of inhibitory/exhaustion markers (PD‐1, TIM3, CD57) were detected on T cells of HIV+ with or without stimulation. The higher expression of exhaustion markers decreased with age and differences diminished in older populations.