A baseline metabolomic signature is associated with immunological CD4 + T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients

Identifier:  imarina:3658269

Handle:  https://hdl.handle.net/20.500.11797/imarina3658269

Authors:  Rodriguez-Gallego, Esther; Gomez, Josep; Pacheco, Yolanda M; Peraire, Joaquim; Vilades, Consuelo; Beltran-Debon, Raul; Mallol, Roger; Lopez-Dupla, Miguel; Veloso, Sergi; Alba, Veronica; Blanco, Julia; Canellas, Nicolau; Rull, Anna; Leal, Manuel; Correig, Xavier; Domingo, Pere; Vidal, Francesc

Abstract:
Objectives: Poor immunological recovery in treated HIV-infected patients is associated with greater morbidity and mortality. To date, predictive biomarkers of this incomplete immune reconstitution have not been established. We aimed to identify a baseline metabolomic signature associated with a poor immunological recovery after ART in order to envisage the underlying mechanistic pathways that influence the treatment response. Design: This was a multi-centre, prospective cohort study in ART-naïve and a pre-ART low nadir (<200 cells/μl) HIV-infected patients (n = 64). Methods: We obtained clinical data and metabolomic profiles for each individual, in which low molecular weight metabolites, lipids and lipoproteins (including particle concentrations and sizes) were measured by nuclear magnetic resonance spectroscopy. Immunological recovery was defined as reaching CD4+ T-cell count ≥250 cells/μL after 36 months of virologically successful ART. We used univariate comparisons, Random Forest test and ROC curves to identify and evaluate the predictive factors of immunological recovery after treatment. Results: HIV-infected patients with a baseline metabolic pattern characterized by high levels of large HDL particles, HDL cholesterol and larger sizes of LDL particles had a better immunological recovery after treatment. Conversely, patients with high ratios of non HDL lipoprotein particles did not experience this full recovery. Medium VLDL particles and glucose increased the classification power of the multivariate model despite not showing any significant differences between the two groups. Conclusions: In HIV-infected patients, a baseline healthier metabolomic profile is related to a better response to ART where the lipoprotein profile, mainly large HDL particles, may play a key