Abstract
BackgroundDespite 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.MethodsA 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.ResultsHerein, 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.ConclusionsThese 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.
Highlights
Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss
Previous studies have shown that even though EC patients are able to suppress HIV replication to an undetectable level, they present different T-cell homeostasis disturbances compared to uninfected controls and/or to HIV non-controllers with suppression of HIV replication mediated by combination antiretroviral therapy [15,16,17,18,19,20], suggesting that Tcell homeostasis disturbances are still operating in EC patients and could potentially be involved in the immunological progression
Of the 36 EC patients included in the study, 22 were considered controls and 14 were considered cases
Summary
Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. There is a small subset of HIV-1+ subjects who are able to spontaneously control HIV-RNA replication in plasma to levels below the limit of detection in the absence of ECs constitute a heterogeneous group in terms of genetic and immunologic characteristics [6], and no single mechanism has been described as being responsible for controlling viral replication [5,6,7] These patients are heterogeneous from the clinical point of view, since some of them show either virologic and/or immunologic progression [8,9,10,11]. Previous studies have shown that even though EC patients are able to suppress HIV replication to an undetectable level, they present different T-cell homeostasis disturbances compared to uninfected controls and/or to HIV non-controllers with suppression of HIV replication mediated by combination antiretroviral therapy (cART) [15,16,17,18,19,20], suggesting that Tcell homeostasis disturbances are still operating in EC patients and could potentially be involved in the immunological progression
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