Human Immunodeficiency Virus Clinical Trial
Official title:
Residual Immune Activation in HIV-infected Patients on Successful cART: Association Between Inflammasome Activation in Monocytes by Circulating Metabolites and Non AIDS Defining Comorbidities
The clinical challenges confronting patients with HIV has shifted over the past 10 years from
acquired immunodeficiency syndrome to chronic diseases including atherosclerosis,
neurocognitive disorders, and osteoporosis. Chronic low grade inflammation and monocyte
activation have been consistently associated with comorbidities in HIV patients. Indeed,
recent studies indicate that inflammatory mediators including IL-6, IL-1, sCD14 and s CD163
produced by monocytes, but not T-cell activation, predict Non-AIDS-related events in
virologically suppressed HIV-infected persons treated with combined antiretroviral therapy
(cART), highlighting the important role of monocyte activation in the occurrence of
comorbidities in cART-treated HIV infected patients. Yet, the underlying molecular pathways
of persistent monocyte activation in cART treated HIV-infected patients remains incompletely
characterized. Our preliminary results: 1/ establish a link between the activation of the
inflammasome, the increased of pyrimidine-derived metabolites and the cardiovascular risk in
a cohort of elderly patients; 2/ show that treated HIV-patients are characterized by
increased soluble IL-1b or IL-18 in their blood suggesting that the inflammasome pathway is
activated.
Objectives: In this study we will characterize the molecular pathways underlying persistent
monocyte activation in treated HIV patients, through the implication of the activation of the
inflammasome machinery: 1. Characterization of NOD like Receptor (NLR) expression in
monocytes for IL-1b and IL-18 secretion (inflammasome activation); 2. Characterization of
circulating metabolites that active the inflammasome machinery; 3. Evaluation of the link
between the activation of the inflammasome, the increased of circulating metabolites and the
non-AIDS related comorbidities.
n/a
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