Frequency of cytokine-producing T cells in HIV-infected patients treated with stavudine, didanosine, and ritonavir

To assess prospectively the influence of the control of viral replication o n the frequency of cytokine-producing T cells, and to correlate these chang es with immune activation, we conducted a 15-month follow-up study of IFN-g amma- and IL-2-producing CD4(+) and CD8(+) T cells at a single-cell level i n 12 previously untreated patients receiving highly active antiretroviral t herapy (HAART). At baseline we observed a strikingly high proportion of IFN -gamma -producing CD8(+) T cells. The treatment-induced decrease in the pro portion of IFN-gamma -producing CD8(+) T cells ran parallel to the decrease in HLA-DR+ and CD38(+)CD8(+) T cell subsets and was associated with the re duction in HIV RNA level. IL-2-producing cells were mainly CD4(+). As a con sequence of CD4(+) T cell loss, the number of IL-2-producing CD4(+) T cells was lower in patients than in control subjects (52 vs. 171 cells/mul), but the proportion of these cells was unchanged (22.4 vs. 19.3). During therap y the proportion of CD4(+) IL-2-producing cells was initially stable and th en fell markedly at month 5, followed by a gradual return to previous value s. The reduction in viral load was associated with the fall in the proporti on of CD4(+) activated subsets. Intracellular cytokine assays are a new app roach to the assessment of T cell function in HIV infection. Our results su ggest that the functional capacity of CD4(+) T cells is probably less sever ely altered than previously thought on the basis of conventional assays. CD 8(+) T cells exhibit an increased capacity to produce IFN-gamma that is ass ociated with an increase in activation marker expression. These alterations decrease partially and in parallel under treatment.