Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children.
OBJECTIVE
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 1 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 1 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.
Hainaut
Marc
M
Department of Pediatrics, Centre Hospitalier Universitaire Saint-Pierre, Free University of Brussels, Belgium.
Ducarme
Martine
M
Schandene
Liliane
L
Peltier
Cecile Alexandra
CA
Marissens
Denise
D
Zissis
Georges
G
Mascart
Francoise
F
Levy
Jack
J
D000293:Adolescent; D000367:Age Factors; D018941:Antigens, CD19 / Q000187:drug effects; D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002176:Candida albicans / Q000737:chemistry / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors
D018941:Antigens, CD19; D015483:HIV Antibodies; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D013745:Tetanus Toxoid; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1