| Publication Abstract Display | | Type: Published Abstract | | Title: Novel biomarkers predictive of non-AIDS events during ART-mediated viral suppression. | | Authors: Hoenigl M, Carlee Moser2, Nicholas Funderburg3, Amy Kantor2, Bosch R, Zhang Y, Eugen-Olsen J, Finkelman M, Landay A, Lederman M, Gianella S | | Year: | | Publication: CROI 2018 | | Volume: Issue: Pages: | | Abstract:Antiretroviral therapy (ART) treated HIV infection is associated with increased risk of morbidity/mortality, and many of these adverse events are associated with increased inflammation. Potential contributors to inflammation include translocation of bacterial and fungal products from the gastrointestinal tract into systemic circulation and pro-inflammatory lipids, but direct linkages between these indices and clinical events have not been adequately demonstrated. Here, in a case/control study, we measured levels of selected plasma biomarkers that have been associated previously with microbial translocation (i.e. lipopolysaccharide binding protein [LBP], beta-D-glucan [BDG], intestinal fatty acid binding protein [I-FABP]), inflammatory lipids (oxidized [ox]LDL), and markers of immune and monocyte activation (soluble urokinase plasminogen activator receptor [suPAR], soluble CD163 [sCD163]), to identify potential associations among levels of these markers and non-AIDS events (myocardial infarction, stroke, cancer, serious bacterial infection and non-accidental death).
Participants (143 cases, 315 controls, 1056 samples) were selected from the ACTG ALLRT trial; all were virally suppressed on ART at year 1, and without subsequent viral failure (Tenorio 2014). Plasma samples were selected: pre-ART initiation, 1-year post-ART, and immediately preceding an event (for cases). Controls had an event-free follow-up equal or greater than that of the relevant case, and participants were matched on age, sex, pre-ART CD4+ count, ART regimen, and parent study. LBP, BDG, I-FABP, sCD163, and oxLDL were measured at all timepoints; suPAR was measured in baseline samples only. At each timepoint, conditional logistic regression analysis assessed associations of the biomarkers with events, and adjusted for relevant covariates.
At baseline, higher levels of suPAR were associated with increased risk of non-AIDS events in both unadjusted and adjusted analyses (Table 1); other biomarkers showed no associations at baseline. At year 1 post-ART and pre-event, higher levels of BDG and LBP were associated with increased risk of non-AIDS events in unadjusted and adjusted analyses. Associations were not observed for I-FABP, sCD163 and oxLDL.
SuPAR, BDG and LBP predicted non-AIDS events and mortality in ART suppressed HIV-infection. These biomarkers may inform future interventional studies aimed at reducing morbidity and mortality in ART-treated HIV infection. |
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