Antiretroviral Treatment of HIV Infection Does Not Influence HIVSpecific Immunity but Has an Impact on Non-Specific Immune Activation

Zofia      Bartovska; Ondrej      Beran; Hanus      Rozsypal; Michal      Holub

Abstract

HIV-specific and non-specific immune responses are crucial in the immunopathogenesis of HIV infection. Therefore, the objective of our study was to analyze the frequency and functional status of HIV-specific CD8+ T cells and the expression of non-specific activation markers on CD8+ T cells in HIV+ patients, and to assess the effects of combined antiretroviral treatment (cART). We examined 28 HIV+ patients, including 13 patients not receiving therapy and 15 patients on cART therapy using ELISpot assay and flow cytometry with intracellular and MHC tetramer staining. MHC tetramers detected HIV-specific CD8+ T cells in 6 HIV+ patients on cART and in 7 untreated individuals; the ELISpot method detected these cells in 5 untreated HIV+ individuals only. Reduced intracellular IFN-γ and IL-2 production by HIV-specific CD8+ T cells was detected in both treated and untreated HIV+ patients, and multifunctional CD8+ T cells simultaneously producing these cytokines were not found in any patient. In contrary to these findings, the percentage of CD8+ T cells expressing CD38 and HLA-DR was significantly higher in untreated patients as compared to HIV+ patients on cART. Together, these results suggest that the alterations of HIV-specific immunity are not influenced by the therapy of HIV infection; whereas, the non-specific chronic immune activation is down-regulated by cART.

Keywords: Antiretroviral therapy, CD38, HIV infection, HIV-specific CD8+ T cells, HLA-DR, multifunctional CD8+ T cells, AIDS, plasma viral load, HIV-1 positive patients, HLA-A2