Development of HIV-1 plasma viral load (RNA-copies per milliliter; ▪), peripheral blood CD4 counts (percent of lymphocytes; •), and sensitivity of CD4⁺ T cells toward anti–APO-1–induced apoptosis (percent CD95-specific cell death; ◊) during highly active antiretroviral therapy (HAART) in 2 children infected perinatally with HIV-1. Patient A was a 10-year-old girl with no previous antiretroviral therapy. After starting HAART using lamivudine, stavudine, and nelfinavir, this patient showed an immediate decrease in sensitivity of CD4⁺ cells toward CD95-induced apoptosis, which was followed by a slow but gradual increase in CD4 counts and a decrease in plasma viral load to levels below the limit of detection (bDNA). Patient B was a 10-year-old boy who switched from combined treatment with zidovudine and lamivudine to HAART using lamivudine, stavudine, and nelfinavir. The reduction in sensitivity of CD4⁺ cells toward CD95-induced apoptosis was somewhat less pronounced, and a considerable increase in CD4 counts was seen only after 8 months of therapy. This patient never achieved complete repression of viral replication during HAART. However, despite the maintenance of high plasma viral load levels, he remained clinically well and showed a further increase in CD4 counts accompanied by the absence of CD95-induced T-cell death in vitro.