Central obesity is a contributor to systemic inflammation and monocyte activation in virally suppressed adults with chronic HIV in Kenya

Abstract

Objectives: Heightened systemic inflammation is common in obese individuals and persons with HIV (PWH) and is independently associated with an increased risk of cardiovascular diseases (CVDs). We investigated the combined effect of central obesity, a surrogate measure of visceral fat and HIV on circulating levels of inflammatory cytokines among Kenyan adults. Design: A cross-sectional study. Methods: We analysed and compared data from 287 virally suppressed PWH and 277 noninfected Kenyan adults, including biomarkers of gut epithelial dysfunction (intestinal fatty acid binding protein), monocyte activation (soluble CD163 and CD14) and inflammation [interleukin (IL)-1β, IL-6, TNF-α and hsCRP] by HIV/central obesity status (HIV-positive/obese, HIV-negative/obese, HIV-positive/nonobese and HIV-negative/nonobese). Central obesity was defined as waist circumference more than 80 cm for women and more than 94 cm for men. We assessed the association of HIV/obesity status with elevated biomarkers (>75th percentile) using logistic regression. Results: Median age for participants was 44 years and 37% were centrally obese. Levels of all biomarkers were higher among the HIV-positive/obese compared with the HIV-negative/nonobese ( P < 0.05 for all comparisons). The HIV-positive/obese group had the greatest odds of having elevated inflammatory biomarkers compared with other groups even after adjustment of age, BMI and other conventional CVD risk factors ( P < 0.05 for all). Additional adjustment for sCD163 in the multivariate model substantially attenuated the association for HIV-positive/obesity with IL-1β, IL-6 and TNF-α but not hsCRP. The contribution of HIV-positive/obesity to inflammation was independent of the degree of immunosuppression. Conclusion: Central obesity is prevalent among virally suppressed African PWH and is associated with greater inflammation and monocyte activation independent of other comorbidities and HIV-specific factors.

Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease

“…PLWH with active and latent tuberculosis have increased levels of immune activation, elevated plasma soluble biomarkers of inflammation, such as sCD14, and increased T-cell activation. 273–277 These elevated biomarkers are indicative of the progression of HIV disease and are associated with a higher risk of mortality. 278,279…”

“…275 In a cohort of African adults living with HIV on ART, latent tuberculosis was associated with immune dysregulation and an increase in markers of inflammation (TNF-α, IL-6, IL-12p70, IL-15, and IL-17A). 276 Some of these markers, such as IL-17A and TNF-α, may promote vascular and endothelial dysfunction, leading to the development and progression of CVD. 167,194,280–282…”

Cardiovascular disease risk in women living with HIV

“…In addition, elevated tissue factor-positive microparticle (MP-TF) activity, a marker of potential clotting risk, was associated with coronary plaque specifically in WLWH in the Women's Interagency HIV Study [60]. Relative increases in inflammatory markers have been tied to obesity in a recent Kenyan cohort, suggesting that there may be additive risk associated with an abnormal body weight among WLWH [61].…”

CD3+T-cell: CD14+monocyte complexes are dynamic and increased with HIV and glucose intolerance

“…Chronic inflammation is linked to diseases like diabetes and atherosclerosis, which can worsen in people living with HIV (PLWH) due to elevated cytokine and chemokine levels despite antiretroviral therapy (ART) (Alcaide et al, 2013; Bailin et al, 2022; Bailin et al, 2020; Grome et al, 2017; Kundu et al, 2022; Temu et al, 2020; Temu et al, 2021; Wanjalla, Mashayekhi, et al, 2021). Traditional analysis of immune cells using flow cytometry often misses interacting cell populations, dismissing cell aggregates as artifacts of sample processing (Hsue & Waters, 2019).…”