Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People

Abstract

HIV-1-infected persons have increased risk of serious non-AIDS events (SNAEs) despite suppressive antiretroviral therapy. Increased circulating levels of soluble CD14 (sCD14), soluble CD163 (sCD163), and interleukin-6 (IL-6) at a single time point have been associated with SNAEs. However, whether changes in these biomarker levels predict SNAEs in HIV-1-infected persons is unknown. We hypothesized that greater decreases in inflammatory biomarkers would be associated with fewer SNAEs. We identified 39 patients with SNAEs, including major cardiovascular events, end stage renal disease, decompensated cirrhosis, non-AIDS-defining malignancies, and death of unknown cause, and age- and sex-matched HIV-1-infected controls. sCD14, sCD163, and IL-6 were measured at study enrollment (T1) and proximal to the event (T2) or equivalent duration in matched controls. Over ∼34 months, unchanged rather than decreasing levels of sCD14 and IL-6 predicted SNAEs. Older age and current illicit substance abuse, but not HCV coinfection, were associated with SNAEs. In a multivariate analysis, older age, illicit substance use, and unchanged IL-6 levels remained significantly associated with SNAEs. Thus, the trajectories of sCD14 and IL-6 levels predict SNAEs. Interventions to decrease illicit substance use may decrease the risk of SNAEs in HIV-1-infected persons.

Immunometabolic and Lipidomic Markers Associated With the Frailty Index and Quality of Life in Aging HIV+ Men on Antiretroviral Therapy

“…In HIV+ people, sCD163 has been associated with risk of obesity and neurocognitive impairment ( Conley et al, 2015 , Burdo et al, 2013 ). Unchanged levels of sCD14 have also been identified as a predictor of serious non-AIDS events ( Sunil et al, 2016 ), but the precise mechanisms of this association are unknown. Our data showing association between frailty and sCD14 are consistent with the findings of the Multicenter AIDS Cohort Study ( Margolick et al, 2017 ), despite this group using a distinctly different measurement of frailty to our study, the Frailty Phenotype.…”

Soluble CD163 Identifies Those at Risk for Increased Hepatic Inflammation & Fibrosis

“…Among HIV-infected persons, serious non-AIDS adverse events (SNAEs; including cardiovascular events [coronary artery disease {CAD} requiring surgery or intervention, myocardial infarction {MI}, cerebrovascular accident or transient ischemic attack {CVA/TIA}, pulmonary embolism {PE}, and cardiac arrest]), end-stage renal disease (ESRD), decompensated cirrhosis, and non-AIDS malignancies were more frequently associated with illicit drug use. Biomarkers that predicted this outcome included failure to see declines in sCD14 and IL-6, while longitudinal changes in sCD163 failed to predict these outcomes, suggesting that at least some of the SNAEs were due to direct organ toxicity effects [ 15 ].…”

A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection

“…The primary endpoint of changes in sCD14 was chosen because levels of this circulating marker of monocyte activation have shown strong association with mortality and morbidity in cohort studies during ART [12,15,16] as well as with key HIV comorbidities [17][18][19][20][21][22][23]. Longitudinal data from the Multicenter AIDS Cohort Study [24] suggest that, among multiple inflammatory biomarkers measured (including CXCL10, interleukin 6, and C-reactive protein), sCD14 fulfills multiple criteria for a highly relevant soluble biomarker.…”