Transient Viral Rebound in Children with Perinatally Acquired HIV-1 Induces a Unique Soluble Immunometabolic Signature Associated with Decreased CD4/CD8 Ratio

Overview

Journal J Pediatric Infect Dis Soc

Publisher Oxford University Press

Specialties Infectious Diseases
Pediatrics

Date 2023 Feb 2

PMID 36727571

Authors

Laura Tarancon-Diez

Joaquim Peraire

Santiago Jimenez de Ory

Maria Guirro

Luis Escosa

Luis Manuel Prieto Tato

Maria Penin Anton

Ana Isabel Piqueras

Alvaro Vazquez Perez

Cesar Gavilan

Matilde Bustillo-Alonso

Maria Luisa Navarro

Consuelo Vilades

Francesc Vidal

Anna Rull

Maria Angeles Munoz-Fernandez

Affiliations

Soon will be listed here.

Abstract

Background: To determine by multi-omic analysis changes in metabolites, lipids, and proteins as a 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 upregulated 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 the 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.

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