RESUMO
People with human immunodeficiency virus (HIV, PWH) face an increased risk of cardiovascular disease (CVD) compared to the general population. We previously demonstrated that people with (versus without) HIV have higher macrophage-specific arterial infiltration in relation to systemic monocyte activation. We now show that select T lymphocyte subpopulations (naïve CD4+, effector memory CD4+, and central memory CD8+) are differentially associated with macrophage-specific arterial infiltration among participants with versus without HIV, with evidence of interaction by HIV status. Our results suggest that among PWH, circulating T lymphocytes associate with macrophage-specific arterial infiltration, of relevance to atherogenesis and CVD risk. CLINICAL TRIALS REGISTRATION: NCT02542371.
RESUMO
Despite antiretroviral therapy (ART), people living with HIV (PLWH) are at increased risk of developing cardiovascular disease (CVD) and HIV-associated neurocognitive disorder (HAND), among other comorbidities. Studies from ART-treated individuals identified galectin-3 (gal-3) and interleukin (IL)-18 as CVD biomarkers, galectin-9 (gal-9) as a HAND biomarker, and sCD163, a marker of monocyte/macrophage activation, as a biomarker of both. We asked if plasma gal-3, gal-9, and IL-18 are associated with an individual comorbidity or increase in both with animals that develop AIDS with both pathologies versus (CVD-path) alone or simian immunodeficiency virus encephalitis (SIVE) alone. We found that no biomarkers were selective between individual pathologies, and all biomarkers increased with co-development of CVD-path and SIVE (gal-3, p = 0.11; gal-9, p = 0.001; IL-18, p = 0.007; sCD163, p < 0.001; %BrdU p = 0.02). Although gal-3, gal-9, and IL-18 did not distinguish between pathologies, they correlated strongly with one another, with sCD163, a marker of monocyte/macrophage activation, and the %BrdU monocytes, a marker of monocyte turnover. Compared to animals with CVD-path or SIVE alone, animals that co-developed both pathologies had consistently elevated IL-18 throughout infection (p = 0.02) and increased sCD163 in late infection (p = 0.01). These data indicate that gal-3, gal-9, and IL-18 are associated with monocyte/macrophage activation by sCD163 and monocyte turnover by the %BrdU+ monocytes more so than CVD-path or SIVE.
RESUMO
Before the antiretroviral therapy (ART) era, people living with HIV (PLWH) experienced complications due to AIDS more so than aging. With ART and the extended lifespan of PLWH, HIV comorbidities also include aging-most likely due to accelerated aging-as well as a cardiovascular, neurocognitive disorders, lung and kidney disease, and malignancies. The broad evidence suggests that HIV with ART is associated with accentuated aging, and that the age-related comorbidities occur earlier, due in part to chronic immune activation, co-infections, and possibly the effects of ART alone. Normally the immune system undergoes alterations of lymphocyte and monocyte populations with aging, that include diminished naïve T- and B-lymphocyte numbers, a reliance on memory lymphocytes, and a skewed production of myeloid cells leading to age-related inflammation, termed "inflamm-aging". Specifically, absolute numbers and relative proportions of monocytes and monocyte subpopulations are skewed with age along with myeloid mitochondrial dysfunction, resulting in increased accumulation of reactive oxygen species (ROS). Additionally, an increase in biomarkers of myeloid activation (IL-6, sCD14, and sCD163) occurs with chronic HIV infection and with age, and may contribute to immunosenescence. Chronic HIV infection accelerates aging; meanwhile, ART treatment may slow age-related acceleration, but is not sufficient to stop aging or age-related comorbidities. Overall, a better understanding of the mechanisms behind accentuated aging with HIV and the effects of myeloid activation and turnover is needed for future therapies.