Highly active antiretroviral therapy (HAART) initiated during acute human immunodeficiency virus (HIV) infection may preserve HIV-specific CD4⁺ T cell responses that are thought to enhance HIV-specific CD8⁺ T cell function. The present pilot study was designed to determine whether preserved HIV-specific immune responses are augmented by the administration of the immunomodulatory agent interleukin (IL)–2. Nine persons recently (<6 months) infected with HIV were randomized to receive HAART alone or HAART plus 3 cycles of intermittent IL-2 during a 12-month period. Although HAART plus IL-2 significantly increased counts of total and naive CD4⁺ T cells, compared with HAART alone, there was no increase in CD4⁺ or CD8⁺ HIV-specific immune responses. In addition, adjuvant IL-2 therapy did not reduce the pool of HIV-infected resting CD4⁺ T cells. Thus, although intermittent IL-2 plus HAART quantitatively increased CD4⁺ T cells, this increase was not selective for HIV-specific CD4⁺ or CD8⁺ T cell responses in recently infected persons