Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children

Objectives. To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age. Methods. All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4(+) and CD8(+) T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year. Results. Nineteen children were evaluated. Naive and memory CD4(+) percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4(+) percentages, naive CD4(+) percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4(+) cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8(+) cells were already decreasing after 3 months, abnormalities of the CD8(+) T cell receptor repertoire and activation of CD8(+) cells persisted at I year. HAART increased the response to mitogens as early as 3 months after starting therapy. Conclusions. In children the recovery of naive CD4(+) cells occurs more rapidly if treatment is started at a younger age, but after I year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8(+) cells persist after 1 year of HAART.