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

Pediatr Infect Dis J. 2003 Jan;22(1):62-9. doi: 10.1097/00006454-200301000-00016.

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Antigens, CD19 / 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
  • Leukocyte Common Antigens / drug effects
  • Male
  • Mitogens / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Receptors, Antigen, T-Cell / immunology
  • Tetanus Toxoid / immunology
  • Time Factors

Substances

  • Antigens, CD19
  • HIV Antibodies
  • Mitogens
  • Receptors, Antigen, T-Cell
  • Tetanus Toxoid
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1