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00925njm 22002777a 4500 dc Benito, José Miguel author Ortiz, María C author León, Agathe author Sarabia, Luis A author Ligos, Jose M. author Montoya, Maria author GarcÍa, Marcial author Ruiz-Mateos, Ezequiel author Palacios, Rosario author Cabello, Alfonso author Restrepo, Clara author Rodríguez, Carmen author Del Romero, Jorge author Leal, Manuel author Muñoz-Fernández, María Ángeles author Alcamí, José author García, Felipe author Górgolas, Miguel author Rallón, Norma author ECRIS author 2018-02 Background: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. Methods: A case-control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares-class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. Results: Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. Conclusions: These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials. BMC Med. 2018 Feb 28;16(1):30. 1741-7015 http://hdl.handle.net/10668/12193 http://hdl.handle.net/20.500.12105/14105 29490663 10.1186/s12916-018-1026-6 1741-7015 BMC Medicine CD4 T-cell loss CD8 exhaustion Class modeling Elite controllers T-cell homeostatic parameters Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers