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Adipokines as New Biomarkers of Immune Recovery : Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy Yeregui, Elena Masip, Jenifer Viladés, Consuelo Domingo, Pere Pacheco, Yolanda M Blanco, Julià Mallolas Masferrer, Josep Alba, Verónica Vargas, Montserrat García-Pardo, Graciano Negredo Puigmal, Eugènia Olona, Montserrat Vidal-González, Judit Peraire, Maria Martí, Anna Reverté Calvet, Laia Gómez-Bertomeu, Fréderic Leal, Manuel Vidal, Francesc Peraire, Joaquim Rull, Anna Universitat Autònoma de Barcelona Adipokines Antiretroviral therapy HIV Immunodiscordant response Poor immune recovery A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4 T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4 T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4 T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4 T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4 T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response. 2022 Article Ministerio de Economía y Competitividad PI16/00503 Ministerio de Economía y Competitividad RD12/0017/0005 Ministerio de Economía y Competitividad RD16/0025/0006 Instituto de Salud Carlos III PI18/01216 Instituto de Salud Carlos III PI19/01337 Instituto de Salud Carlos III PI20/00326 International journal of molecular sciences ; Vol. 23 Núm. 4 (2-2 2022), p. 2202 open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/