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 on the frequency of cytokine-producing T cells, and to correlate these changes with immune activation, we conducted a 15-month follow-up study of IFN-γ- and IL-2-producing CD4⁺ and CD8⁺ T cells at a single-cell level in 12 previously untreated patients receiving highly active antiretroviral therapy (HAART). At baseline we observed a strikingly high proportion of IFN-γ-producing CD8⁺ T cells. The treatment-induced decrease in the proportion of IFN-γ-producing CD8⁺ T cells ran parallel to the decrease in HLA-DR⁺ and CD38⁺ CD8⁺ T cell subsets and was associated with the reduction in HIV RNA level. IL-2-producing cells were mainly CD4⁺. As a consequence 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/μl), but the proportion of these cells was unchanged (22.4 vs. 19.3). During therapy the proportion of CD4⁺ IL-2-producing cells was initially stable and then fell markedly at month 5, followed by a gradual return to previous values. The reduction in viral load was associated with the fall in the proportion of CD4⁺ activated subsets. Intracellular cytokine assays are a new approach to the assessment of T cell function in HIV infection. Our results suggest that the functional capacity of CD4⁺ T cells is probably less severely altered than previously thought on the basis of conventional assays. CD8⁺ T cells exhibit an increased capacity to produce IFN-γ that is associated with an increase in activation marker expression. These alterations decrease partially and in parallel under treatment.