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Obesity and chronic, treated HIV infection are both associated with persistent systemic inflammation and a similar constellation of metabolic and cardiovascular diseases, but the combined effects of excess adiposity and HIV on circulating proinflammatory cytokines and other biomarkers previously shown to predict disease risk is not well described. We measured inflammation biomarker levels in 158 predominantly virologically suppressed adults on long-term antiretroviral therapy (ART) with a range of body mass index (BMI) values from normal to morbidly obese. We assessed the relationship between BMI and each biomarker using multivariable linear regression adjusted for age, sex, race, CD4(+) count, tobacco use, data source, protease inhibitor use, and routine nonsteroidal antiinflammatory drug (NSAID) or aspirin use. Among normal-weight (n=48) and overweight participants (n=41; BMI <30 kg/m(2)), incremental BMI increases were associated with significantly higher serum highly sensitive C-reactive protein (hsCRP; β=2.47, p=0.02) and tumor necrosis factor (TNF)-α receptor 1 levels (β=1.53, p=0.03), and significantly lower CD14 levels (β=0.84, p=0.01), but similar associations were not observed in the obese participants. Among the obese (n=69; BMI ≥30 kg/m(2)), however, higher serum levels of interleukin-6 (IL-6; β=1.30, p=0.02) and macrophage inflammatory protein-1α (β=1.77, p<0.01) were associated with higher BMI, a finding not observed among the nonobese. Among all participants, IL-6 and TNF-α receptor 1 levels were most closely associated with hsCRP (p<0.01). Further studies are needed to determine whether higher serum inflammation biomarker levels found in obese HIV-infected individuals on ART reflect an increased likelihood of adverse health outcomes, or if novel markers to estimate mortality and disease risk are needed in this population.