An observational study of children vertically infected with human immunodeficiency virus type 1 (HIV-1) was performed to determine the role of CD38 expression in CD8(+) T cells as prognostic marker of virological failure in children receiving HAART. We studied 42 children who were receiving antiretroviral therapy and who had an undetectable virus load (uVL), and we found a negative correlation between CD38 expression in CD8(+) T cells and the duration of uVL. We selected 17 HIV-1-infected children with CD38 values close to the baseline level (i.e., the first uVL achieved), and we distributed the children into 2 groups on the basis of median CD38 value in CD8(+) T cells. Children with CD38 values in CD8(+) T cells that were higher than the median had a higher incidence and relative risk of virological failure than did those with values lower than the median. In conclusion, we demonstrate for the first time that CD8(+)CD38(+) T cell count is a good prognostic marker of therapeutic failure in HIV-1-infected children.