Our objective was to study the probability of achieving undetectable viral load levels in HIV-1-infected children after 36 mo of highly active antiretroviral therapy (HAART). A prospective, multicenter, longitudinal study in 41 HIV-1-infected children on HAART was undertaken. Viral load was quantified using standard molecular assay. CD4+ and CD8+ T cell subsets were determined by flow cytometry. The probability of achieving undetectable viral load was determined using Kaplan-Meier curves according to groups by percentage CD8+ at baseline (CD8+ <25% or >25%). Lower baseline CD8+ T cell levels conditioned a less effective virological response to HAART in children, independent of baseline CD4+ T cell numbers and viral load levels. A greater number of children (81%) from CD8+ >25% group than from the CD8+ <25% (40%) presented undetectable viral load levels (p = 0.013). Additionally, the CD8+ >25% group showed a 4.5-fold higher (95% confidence interval: 1.1-19.2) relative proportion for achieving viral load <400 copies/mL than the CD8+ <25% group (p = 0.039). We concluded that monitoring CD8+ T cell numbers may be valuable in deciding when to start HAART in vertically HIV-1-infected children.