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CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy.
J Acquir Immune Defic Syndr 2006; 42(3):269-76JA

Abstract

OBJECTIVE

The aim of this study was to analyze the association between CD4(+) depletion and immune activation in HIV-1-infected children on highly active antiretroviral therapy (HAART).

DESIGN AND SETTING

We carried out a cross-sectional study to determine the profile of several immunologic parameters in 143 children on HAART for more than 24 weeks. Children were stratified according to current immunologic status (CD4 < or =15%, 15%-25%, and > or =25%) and viral load (VL) levels (<400 copies/mL; 400-10,000 copies/mL; and >10,000 copies/mL). We also studied 23 uninfected children as healthy controls.

METHODS

Viral load (HIV-RNA copies per milliliter) was quantified using reverse transcriptase polymerase chain reaction molecular assay. T-cell subsets were determined by multiparametric flow cytometry.

RESULTS

HIV-infected children with low percentage of CD4(+) had high memory (CD45RO(+)) and low naive (CD45RA(+)) CD4(+) and CD8(+) T-cell values. Furthermore, children with CD4(+) >25% had similar memory and naive CD4(+) values as the healthy control group, whereas memory and naive CD8(+) subsets were different from the healthy control values. In these HIV-infected children, when CD4(+) was depleted, the amount of naive plus central memory CD8(+) (CD28(+)CD57(-)) cells was decreased, whereas effector CD8(+) (CD28(-)CD57(+)) cells were upregulated, and these values were always higher than healthy control values. Furthermore, children with low percentage of CD4(+) showed significant upregulation of HLA-DR(+)CD38(+) and HLA-DR(+) in both CD4(+) and CD8(+) T-cells independent of VL levels.

CONCLUSIONS

Our data suggest that elevated immune activation could be responsible for CD4(+) depletion rather than HIV replication because immunologic status is associated directly to immune activation and not to VL levels in HIV-infected children on HAART.

Authors+Show Affiliations

Laboratorio de Inmuno-Biología Molecular, Hospital Universitario "Virgen de Rocío," Sevilla, Spain. sresino.hgugm@salud.madrid.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16810122

Citation

Resino, Salvador, et al. "CD4(+) T-cell Immunodeficiency Is More Dependent On Immune Activation Than Viral Load in HIV-infected Children On Highly Active Antiretroviral Therapy." Journal of Acquired Immune Deficiency Syndromes (1999), vol. 42, no. 3, 2006, pp. 269-76.
Resino S, Seoane E, Gutiérrez MD, et al. CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2006;42(3):269-76.
Resino, S., Seoane, E., Gutiérrez, M. D., León, J. A., & Muñoz-Fernández, M. A. (2006). CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes (1999), 42(3), pp. 269-76.
Resino S, et al. CD4(+) T-cell Immunodeficiency Is More Dependent On Immune Activation Than Viral Load in HIV-infected Children On Highly Active Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2006;42(3):269-76. PubMed PMID: 16810122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy. AU - Resino,Salvador, AU - Seoane,Elena, AU - Gutiérrez,Maria Dolores Gurbindo, AU - León,Juan Antonio, AU - Muñoz-Fernández,Maria Angeles, PY - 2006/7/1/pubmed PY - 2006/8/12/medline PY - 2006/7/1/entrez SP - 269 EP - 76 JF - Journal of acquired immune deficiency syndromes (1999) JO - J. Acquir. Immune Defic. Syndr. VL - 42 IS - 3 N2 - OBJECTIVE: The aim of this study was to analyze the association between CD4(+) depletion and immune activation in HIV-1-infected children on highly active antiretroviral therapy (HAART). DESIGN AND SETTING: We carried out a cross-sectional study to determine the profile of several immunologic parameters in 143 children on HAART for more than 24 weeks. Children were stratified according to current immunologic status (CD4 < or =15%, 15%-25%, and > or =25%) and viral load (VL) levels (<400 copies/mL; 400-10,000 copies/mL; and >10,000 copies/mL). We also studied 23 uninfected children as healthy controls. METHODS: Viral load (HIV-RNA copies per milliliter) was quantified using reverse transcriptase polymerase chain reaction molecular assay. T-cell subsets were determined by multiparametric flow cytometry. RESULTS: HIV-infected children with low percentage of CD4(+) had high memory (CD45RO(+)) and low naive (CD45RA(+)) CD4(+) and CD8(+) T-cell values. Furthermore, children with CD4(+) >25% had similar memory and naive CD4(+) values as the healthy control group, whereas memory and naive CD8(+) subsets were different from the healthy control values. In these HIV-infected children, when CD4(+) was depleted, the amount of naive plus central memory CD8(+) (CD28(+)CD57(-)) cells was decreased, whereas effector CD8(+) (CD28(-)CD57(+)) cells were upregulated, and these values were always higher than healthy control values. Furthermore, children with low percentage of CD4(+) showed significant upregulation of HLA-DR(+)CD38(+) and HLA-DR(+) in both CD4(+) and CD8(+) T-cells independent of VL levels. CONCLUSIONS: Our data suggest that elevated immune activation could be responsible for CD4(+) depletion rather than HIV replication because immunologic status is associated directly to immune activation and not to VL levels in HIV-infected children on HAART. SN - 1525-4135 UR - https://www.unboundmedicine.com/medline/citation/16810122/CD4_+__T_cell_immunodeficiency_is_more_dependent_on_immune_activation_than_viral_load_in_HIV_infected_children_on_highly_active_antiretroviral_therapy_ L2 - http://Insights.ovid.com/pubmed?pmid=16810122 DB - PRIME DP - Unbound Medicine ER -