A baseline metabolomic signature is associated with immunological CD4(+) T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients
Por:
Rodriguez-Gallego, E, Gomez, J, Pacheco, YM, Peraire, J, Vilades, C, Beltran-Debon, R, Mallol, R, Lopez-Dupla, M, Veloso, S, Alba, V, Blanco, J, Canellas, N, Rull, A, Leal, M, Correig, X, Domingo, P, Vidal, F
Publicada:
13 mar 2018
Resumen:
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 antiretroviral therapy (ART) to envisage the underlying mechanistic pathways that influence the treatment response.Design:This was a multicentre, prospective cohort study in ART-naive and a pre-ART low nadir (<200 cells/l) 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 NMR spectroscopy. Immunological recovery was defined as reaching CD4(+) T-cell count at least 250 cells/l after 36 months of virologically successful ART. We used univariate comparisons, Random Forest test and receiver-operating characteristic 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 high density lipoprotein (HDL) particles, HDL cholesterol and larger sizes of low density lipoprotein 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 very-low-density lipoprotein particles and glucose increased the classification power of the multivariate model despite not showing any significant differences between the two groups.Conclusion: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 role.
Filiaciones:
Rodriguez-Gallego, E:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Gomez, J:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Rovira & Virgili Univ, IISPV, Dept Elect Engn, Metabol Platform, Tarragona, Spain
Pacheco, YM:
Univ Seville, Virgen del Rocio Univ Hosp, CSIC,Inst Biomed Seville,IBiS, Lab Immunovirol,Clin Unit Infect Dis Microbiol &, Seville, Spain
Peraire, J:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Vilades, C:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Beltran-Debon, R:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Mallol, R:
Rovira & Virgili Univ, IISPV, Dept Elect Engn, Metabol Platform, Tarragona, Spain
Lopez-Dupla, M:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Veloso, S:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Alba, V:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Blanco, J:
Univ Autonoma Barcelona, IGTP, AIDS Res Inst IrsiCaixa, Badalona, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
Canellas, N:
Rovira & Virgili Univ, IISPV, Dept Elect Engn, Metabol Platform, Tarragona, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid, Spain
Rull, A:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Leal, M:
Univ Seville, Virgen del Rocio Univ Hosp, CSIC,Inst Biomed Seville,IBiS, Lab Immunovirol,Clin Unit Infect Dis Microbiol &, Seville, Spain
Correig, X:
Rovira & Virgili Univ, IISPV, Dept Elect Engn, Metabol Platform, Tarragona, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid, Spain
Domingo, P:
Hosp Santa Creu & Sant Pau, Dept Internal Med, HIV Unit, Barcelona, Spain
Vidal, F:
Univ Rovira & Virgili, Hosp Univ Joan 23, IISPV, Dept Internal Med & Infect Dis,HIV Unit, Tarragona, Spain
Green Published
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