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The present study was designed to determine the effect of immune activation, achieved by influenza vaccination, on plasma HIV RNA levels and immunological parameters including CD4 cell levels, antigen-stimulated T-cell function and apoptotic death of peripheral blood mononuclear cells.Thirty-four HIV-infected individuals and nine uninfected controls were immunized with influenza vaccine and blood was collected at weeks 0, 2, 4 and 16. Plasma was isolated and used for HIV RNA and influenza-specific antibody quantifications. CD4 cell counts, activation and maturation markers of T-lymphocyte subsets were determined by flow cytometry. In vitro T-helper responses, spontaneous- and activation-induced cell death assays were also performed.Influenza-specific humoral and cellular immune responses correlated with CD4 count. Only in patients with CD4 counts > 300 × 106/l there was a modest increase in T-cell responses to influenza virus, which was less than control subjects, observed after vaccination. Immunization had no significant effect on CD4 counts or plasma viral levels in the HIV-positive patients. Baseline apoptosis inversely correlated with CD4 counts and directly correlated with viral load. Activation-induced apoptosis did not change appreciably after vaccination and spontaneous apoptosis increased only in the < 300 CD4 group.These results indicate that immune stimulation resulting from influenza vaccination did not significantly change the levels of plasma virus, CD4 cell counts, or activation-induced apoptosis in HIV-infected individuals, although an increase in the T-cell response to influenza and spontaneous apoptosis was observed in the > 300 and < 300 CD4 groups, respectively.