Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children.
Abstract
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 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.Clinical TrialControlled Clinical TrialJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe- info:eu-repo/semantics/article
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- Sciences bio-médicales et agricoles
- Adolescent
- Age Factors
- Antigens, CD19 -- drug effects
- Antigens, CD45 -- drug effects
- Antiretroviral Therapy, Highly Active
- CD4-CD8 Ratio
- CD4-Positive T-Lymphocytes -- immunology
- CD8-Positive T-Lymphocytes -- drug effects
- Candida albicans -- chemistry
- Candida albicans -- immunology
- Female
- HIV Antibodies -- analysis
- HIV Infections -- drug therapy
- HIV Infections -- immunology
- HIV-1 -- immunology
- HIV-1 -- isolation & purification
- Humans
- Infant
- Male
- Mitogens -- immunology
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
- Receptors, Antigen, T-Cell -- immunology
- Tetanus Toxoid -- immunology
- Time Factors
- Age
- CD4
- CD8
- Highly active antiretroviral therapy
- Human immunodeficiency virus type 1-infected children
- Immune reconstitution