Analysis of the effect of highly active antiretroviral therapy during acute HIV-1 infection on HIV-specific CD4 T cell functions

Abstract

Early HAART during acute HIV-1 infection resulted in higher numbers of HIV-specific IFN-gamma- and IL-2-producing CD4 T cells, but this preservation in four out of five patients was not associated with control of viraemia upon treatment interruption.

Defective Human Immunodeficiency Virus-Specific CD8 + T-Cell Polyfunctionality, Proliferation, and Cytotoxicity Are Not Restored by Antiretroviral Therapy

“…Diminished in vitro function during HIV viremia and restoration during ART have now been described for a wide array of immune system cells and functions. These include proliferation, IL-2 production, and CCR7 expression of HIV-specific CD4 ϩ T cells (16,18,20,37,46,50). In one recent longitudinal study, restoration of multiple functions of the HIV-specific CD8 ϩ T cells of chronically infected progressors was also observed after 26 weeks of ART (41).…”

“…We also previously observed that the proliferative capacity and cytotoxic responses of HIV-specific CD8 ϩ T cells in a subset of treated progressors with antiretroviral-induced suppression of HIV viremia (Rx Ͻ50) were significantly lower than those measured in LTNP (29,30). However, it remained unclear whether increases in CD4 ϩ T-cell proliferation or IL-2 production observed in treated patients in cross-sectional and longitudinal cohorts would translate into increased CD8 ϩ Tcell proliferative or cytotoxic capacities (16,18,20,24,37,46,50). In the present study, we recruited a larger number of Rx Ͻ50, with HIV RNA levels suppressed to Ͻ50 copies/ml for a median of 5 years, to determine the impact of reduced antigen load and immune activation on HIV-specific CD4 ϩ and CD8 ϩ T-cell function.…”

“…High levels of antigen can have potent effects on diverse cell types in humans and in animal models. For HIV, lowering the level of viremia through ART has been observed to increase the function of CD4 ϩ and CD8 ϩ T cells, NK cells, monocytes, and plasmacytoid dendritic cells (16,18,20,37,41,(45)(46)(47)50). However, the vast majority of treated progressors will not control HIV replication when ART is interrupted (7,9,35), suggesting that many of the qualitative differences in the CD4 ϩ or CD8…”

“…In some but not all studies, ART was sufficient to restore the proliferative capacity, phenotype, and cytokine production by CD4 ϩ T cells to levels similar to responses to other viruses or to the HIV-specific response of LTNP (13,16,18,20,37,46,50). Because better IL-2 production or function of HIV-specific CD4 ϩ T cells has been associated with increased CD8 ϩ T-cell proliferative capacity (24), it has also been suggested that diminished proliferative capacity of progressor CD8 ϩ T cells may be an effect of viremia during the chronic phase of infection.…”

Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

“…Following HIV infection, progression to AIDS is typically associated with chronic immune activation that gradually depletes the naïve CD4 1 T-and CD8 1 T-cell pools and subsequently impairs the immune function of HIV-specific CD4 1 and CD8 1 T cells. [17][18][19] To date, the contribution of Vd 2 T-cell depletion in chronic immune activation has not been comprehensively investigated in HIV infection. In this study, we performed a comprehensive phenotypic and functional analysis of memory cd T cells in cohorts of Chinese individuals with acute and chronic HIV infection in different stages of progression to define the specificity of Vd 2 T-cell depletion and the functional changes in the cd subsets.…”