Differential effect of HAART on CD4 and CD8 T-cell cytokine production and response to CMV antigens in HIV+ patients
Abstract number: 10.1111/j.1198-743X.2004.902_o129.x
To determine the effect of HAART on cytokine production and response to CMV antigens in CD4+ and CD8+ T-cells in HIV+ patients no on anti-retroviral therapy and following initiation of HAART.
A total of 73 patients with HIV infection were divided into those stable without HAART and those on HAART. Patients on HAART were divided further on the basis of their length of time on HAART (> or <3 months), viral load (> or <50 copies/mL, CD4 count nadir and whether their CD4 count had increased to >150 cells/mL on HAART, gender and origin. CD4+ and CD8+ T-lymphocyte cytokine production in response to stimulation with PMA and ionomycin using single cell flow cytometry was performed. In a further cohort of 104 CMV+/HIV+ patients on HAART, proliferative and cytokine responses to CMV antigens were analysed and compared.
CD4+ and CD8+ IFNg expression was increased in HIV+ groups when compared with controls. CD4+ cell IFNg expression normalized on HAART when CD4 count was >150 cells/mL. CD4+ IL-2 expression was significantly reduced in all HIV patients when compared with controls and did not significantly improve on HAART. However IL-2 production by CD8 cells was significantly improved in all patients on HAART when compared with HIV patients on no HAART. This was normalized in patients following HAART for 3 months or greater, when their CD4 count exceeded 150 cells/mL or when the HIV viral load was <50 copies/mL. In response to CMV antigens, all groups showed a significant reduction in CD4+ T-cell function and production of cytokines, despite an increase in absolute CD4+ T-cell numbers. By contrast in patients responding to HAART, CMV-specific CD8+ T-cells have increased responses to CMV.
These results show that the production of IL-2 by CD8 cells and IFNg by CD4+ cells becomes normalized on successful HAART and that even at low CD4+ counts CD8+ responses to CMV are enhanced. This is likely to account for the early clinical improvement in rate of opportunistic infections and reduced risk of death in patients on HAART."
|Session name:||XXIst ISTH Congress|
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