LAUSR

BACKGROUND To determine by multi-omic analysis changes in metabolites, lipids and proteins as consequence of transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV). METHODS Plasma samples from children with PHIV and with tVR (first episode of transient RNA-HIV viral load >20 copies/ml followed by suppression) on the time-point immediately before (pre-tVR) and after (post-tVR) the tVR were assessed. Multi-omic analyses were performed using nLC-Orbitrap, GC-qTOF-MS and LC-qTOF-MS. RESULTS Comparing pre- and post-tVR time-points, HIV-1-children with tVR (n=5) showed a trend to a decrease in ratio CD4/CD8 (p=0.08) but no significant differences were observed in plasma metabolites, lipids or proteins. Post-tVR condition was compared with a reference group of children with PHIV with persistent viral control (n=9), paired by sex, age and time under antiretroviral treatment. A total of 10 proteins, 8 metabolites and 2 lipids showed significant differences (p<0.05): serotransferrin, clusterin, kininogen-1, succinic acid, threonine, 2-hydroxyisovaleric acid, methionine, 2-hydroxyglutaric, triacylglyceride 50:0 (TG50:0) and diacylglyceride 34:1 (DG34:1) were up-regulated while alpha-2-macroglobulin, apolipoprotein A-II, carboxylic ester hydrolase, apolipoprotein D, coagulation factor IX, peptidase inhibitor 16, SAA2-SAA4 readthrough, oleic acid, palmitoleic acid and D-sucrose downregulated on post-tVR time-point compared to reference group. Ratio CD4/CD8 correlated with apolipoprotein A-II, DG34:1 and methionine (p=0.004;ρ=0.71, p=0.016;ρ=-0.63 and p=0.032;ρ=-0.57, respectively). Nadir CD4+ correlated inversely with kininogen-1 (p=0.022;ρ=-0.60) and positively with D-sucrose (p=0.001;ρ=0.77). CONCLUSIONS tVR followed by suppression implies changes in soluble proteins, lipids and metabolites that correlate with immunological parameters, mainly ratio CD4/CD8, that decreased after tVR. These distinct soluble biomarkers could be considered potential biomarkers of immune progression.