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Characterizing immune reconstitution after long-term highly active antiretroviral therapy in pediatric AIDS
Salvador Resino1, Rafael Correa, José M Bellón
1Department of Immunology, General University Hospital Gregorio Marañón, 28007 Madrid, Spain.
Insights
Children with vertically acquired HIV-1 infection who respond to highly active antiretroviral therapy (HAART) show significant immune system recovery. Their T cell function and counts can normalize, resembling uninfected children.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Vertical HIV-1 infection poses significant challenges to T lymphocyte recovery.
- Highly active antiretroviral therapy (HAART) is crucial for managing HIV-1 in children.
- Understanding T cell dynamics in response to HAART is vital for long-term prognosis.
Purpose of the Study:
- To characterize T lymphocyte recovery in vertically HIV-1-infected children undergoing long-term HAART.
- To compare immune recovery in children responsive versus non-responsive to HAART.
- To evaluate T cell subset production and function in HIV-1-infected children.
Main Methods:
- A 3-year longitudinal retrospective study of 32 vertically HIV-1-infected children.
- Categorization into long-term asymptomatic, HAART-responsive, and HAART-non-responsive groups.
- Assessment of T cell subsets, lymphoproliferative responses (LPRs), and T cell receptor rearrangement excision circles (TRECs).
Main Results:
- HAART-responsive children showed increased CD4(+) T cells, decreased viral load, and recovered LPRs.
- The responsive group exhibited naive T cell production and TREC levels similar to long-term asymptomatic children.
- Immune recovery in responsive children approached levels seen in healthy, uninfected controls.
Conclusions:
- Children with vertically acquired HIV-1 infection who respond to HAART can achieve significant immune recovery.
- Quantitative and functional immune parameters can normalize, resembling non-progressors or uninfected children.
- This highlights the potential for robust immune reconstitution with effective antiretroviral therapy.
Abstract:
In this study, we sought to characterize the T lymphocyte recovery in vertically HIV-1-infected children who respond to long-term highly active antiretroviral therapy (HAART). A 3-year longitudinal retrospective study was used to perform a cross-sectional study of 32 children rated according to the time course of CD4(+) T cell percentages in response to antiretroviral therapy and CDC clinical classification: (1) long-term asymptomatic (LTA group): 8 children in A1 during the whole follow-up period; (2) responsive to HAART (Rec group): 13 children in C3 before HAART who achieved CD4(+) T cell counts of > 500 cells/mm(3) after 3 years of HAART; and (3) nonresponsive to HAART (Non-Rec group): 11 children in C3 during the whole follow-up period despite 3 years of HAART. We also studied 17 healthy age-matched uninfected children as controls. Lymphoproliferative responses (LPRs) were evaluated by incorporation of [(3)H]thymidine, identification of T cell subsets by three-color flow cytometry, and determination of thymic production of T cells by quantification of T cell receptor rearrangement excision circles (TRECs). Interestingly, the Rec group showed an increase in percentage of CD4(+) T cells and a decrease in viral load, and recovered LPRs to mitogens and recall antigens, with values similar to those of the LTA group. Moreover, the Rec group produced similar percentages and absolute counts of naive (CD45RA(+)CD62L(+)) CD4(+) and CD8(+) T cells, and TRECs similar to those of the LTA group. In particular, the Rec group produced similar percentages of CD8(+)CD28(-)CD57(+) and CD8(+)CD28(-)CD57(-) T cell subsets compared with controls. Our data indicate that among children who have already progressed to AIDS and severe immunodeficiency but who respond to HAART, the immune system can recover and resemble those of nonprogressors or even uninfected children, in quantitative as well as in functional terms.