This study evaluates the change in CD4(+) T cell counts among patients who achieved complete viral suppression and subsequently discontinued highly active antiretroviral therapy (HAART). We included 72 human immunodeficiency virus (HIV)-1-infected patients with plasma HIV RNA loads of <500 copies/mL for at least 3 months who then discontinued therapy for at least 12 weeks. The median CD4(+) T decay while off HAART was 16 cells/mm(3)/month (interquartile range, -6 to -34 cells/month). The mean follow-up after therapy ended was 45 weeks. The slope of the CD4(+) T cell decay was inversely correlated with the increase of CD4(+) T cells while receiving HAART, baseline virus load, CD4(+) T cell count at the time therapy was discontinued, age, and duration HIV RNA levels were undetectable. In a multiple regression analysis model, the increase of CD4(+) T cells while receiving therapy and age were independently associated with the rate of CD4(+) T cell loss.