A previous study showed that, during the first year of life, the presence of cytotoxic T lymphocytes (CTLs) in human immunodeficiency virus (HIV)-infected children is associated with a lack of rapid progression to acquired immunodeficiency syndrome. The goal of the study was to address the role of CTLs in children who survived after age 5 years. Memory HIV-specific CTLs directed against Env, Gag, Nef, and Pol proteins were measured in a group of 47 highly active antiretroviral therapy-naive HIV-infected children. Both Gag- and Pol-specific CTLs were positively correlated with CD4(+) T cell counts. Gag-, Nef-, and Pol-specific CTLs were inversely correlated with virus load. The inverse correlation between virus load and Gag-specific CTLs was independent of CD4(+) T cell counts. In conclusion, this study showed the beneficial role of HIV-specific CTLs in children who survived after age 5 years.