HIV infection is characterized by a decrease in total CD4 cell count, rising viral load, as well as an increase in immune activation levels. Increased activation can lead to an increase in apoptosis and contribute to CD4 depletion. We evaluated the clinical and immunologic responses of 23 HIV-positive Ugandan volunteers following initiation of antiretroviral therapy (ART). All volunteers achieved and maintained complete viral suppression within the first 3 months of therapy (p > 0.05). CD4+ and CD8+ T cell activation also decreased significantly, although it never reached the level of HIV negative Ugandan volunteers. Viral suppression and CD4 cell recovery were also associated with an improved profile in CD8+ T cell functional markers, but had no effect on HIV-specific proliferation. We conclude that ART in a cohort of therapy-naive Ugandans with AIDS partially restores but does not fully reverse the immune dysfunction observed in chronic HIV infection.