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The influence of CD4(+) T cell nadirs on human immunodeficiency virus (HIV)-specific immune responses in subjects with apparently normal CD4(+) T cell counts is not known. We evaluated the frequency of HIV-1-specific immune responses in a cohort of patients with complete viral suppression (HIV-1 RNA load, <50 copies/mL) who were receiving highly active antiretroviral therapy and had a wide range of CD4(+) T cell nadirs. We found positive associations between CD4(+) T cell nadirs and the magnitude of HIV-specific CD8(+) T cell responses (P=.02) and of T cell helper responses (P=.04). These data show the CD4(+) T cell nadir to be an independent predictor of HIV-specific CD4(+) and CD8(+) T cell responses in HIV-1-infected subjects with optimal suppression of viremia. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]