Early treatment intervention during human immunodeficiency virus (HIV) infection is a strategy aimed to preserve and/or enhance the developing anti-HIV immune responses. We report the effect of highly active antiretroviral therapy (HAART) combined with intermittent subcutaneous doses of Interleukin 2 (IL-2) on CD8(+) cell noncytotoxic anti-HIV responses (CNAR), as well as on viral loads and CD4(+) cell/CD8(+) cell numbers in subjects with primary HIV-1 infection. Twenty-four patients received HAART, 24 received a combination of HAART plus IL-2, and 12 elected no-therapy. In comparison to HAART alone, IL-2 treatment led to significant increases in CD4(+) cell numbers through week 48 of the study. No effect was observed on viral loads or the CD8(+) cell population. The first cycle of IL-2 enhanced CNAR; later cycles showed no substantial effect. This study suggests that HAART combined with IL-2 could provide an immunologic benefit in the treatment of early HIV infection.