Higher levels of IL-6, CD4 turnover and Treg frequency are already present before cART in HIV-infected subjects with later low CD4 recovery

• Published in: Antiviral research 2017-06, Vol.142, p.76-82
• Main Authors: Rosado-Sánchez, Isaac, Jarrín, Inmaculada, Pozo-Balado, María M., de Pablo-Bernal, Rebeca S., Herrero-Fernández, Inés, Alvarez-Ríos, Ana I., Rodríguez-Gallego, Esther, Genebat, Miguel, Vera, Mar, Berenguer, Juan, Martín, María L., Bernal, Enrique, Vidal, Francesc, Blanco, Julià, Leal, Manuel, Pacheco, Yolanda M.
• Format: Article
• Language: English
• Subjects: Adult; Antiretroviral Therapy, Highly Active; cART; Case-Control Studies; CD4 Lymphocyte Count; CD4 T-cell homeostasis; CD4-Positive T-Lymphocytes - metabolism; fas Receptor - metabolism; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1; Homeostasis; Humans; Inflammation; Inflammation - immunology; Interleukin-6 - metabolism; Ki-67 Antigen - metabolism; Low CD4 recovery; Lymphocyte Activation - immunology; Male; Middle Aged; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Treg; Turnover
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.03.015

Immunological characterization of HIV-infected subjects with low CD4-recovery (LR-subjects) has been extensively performed after a variable period of combined antiretroviral therapy (cART). We now explore immunological alterations present before the cART onset. In a case-control study, we selected pre-cART samples of HIV-subjects with and without low CD4-recovery after cART (n = 21 per group). CD4 T-cell activation, senescence and exhaustion related markers were not found specifically altered before cART initiation. On the other hand, we found that LR-subjects before cART already showed increased levels of IL6 (p = 0.009) and increased frequencies of Ki67+CD4+ T-cells (p = 0.026), CD45RA-CD27+CD4+ T-cells (p = 0.008) and Treg (p = 0.001), as well as increased expression of CD95 and CD127 on CD4 T-cells (p = 0.016; p = 0.032, respectively). These parameters characterize the immunological damage in LR-subjects before the cART onset and could be associated to the mechanisms hindering the subsequent CD4 recovery. •We analyzed before-to-cART immunological alterations in HIV-subjects with low CD4-recovery after cART.•Before the cART onset, LR-subjects did not show several known homeostatic alterations characterizing them after cART.•Before cART onset, LR subjects showed increased levels of IL-6, Treg and expression of Ki67 and CD95 in CD4 T-cells.