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Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active
1Immunobiology Molecular Laboratory, Hospital General Universitario Gregorio Maranón Madrid, Spain.
Insights
Highly active antiretroviral therapy (HAART) improved immune function in HIV-infected children by increasing T cell receptor excision circle (TREC) levels and naive T cell counts. This immune reconstitution led to better responses to mitogens and cytokines after one year of treatment.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- HIV infection in children leads to moderate or severe immunodeficiency.
- Highly active antiretroviral therapy (HAART) is a standard treatment for pediatric HIV.
- Monitoring immune system changes after HAART is crucial for assessing treatment efficacy.
Purpose of the Study:
- To monitor immune system changes in HIV-infected children with immunodeficiency after HAART.
- To evaluate the impact of HAART on T cell subsets, cytokine production, and antibody levels.
- To correlate T cell receptor excision circle (TREC) levels with immune cell counts.
Main Methods:
- Follow-up study of 14 HIV-infected children on HAART over approximately 11.8 months.
- Measurement of T cell receptor excision circle (TREC) levels, viral load (VL), and CD4(+) and CD8(+) T cell subsets.
- Assessment of lymphoproliferative responses to pokeweed mitogen (PWM) and cytokine production (TNF-alpha, IFN-gamma).
- Quantification of IgG, IgG(1), and IgG(3) plasma levels.
Main Results:
- TREC levels significantly increased after HAART, correlating positively with CD4(+) T cell counts and percentages.
- Naive CD4(+) and CD8(+) T cell subsets increased significantly, with some subsets reaching control group levels.
- Lymphoproliferative responses and cytokine production (TNF-alpha, IFN-gamma) recovered to normal levels after one year on HAART.
- Viral load did not change significantly, while IgG, IgG(1), and IgG(3) levels decreased.
Conclusions:
- HAART induces immune system reconstitution in HIV-infected children.
- Immune recovery is characterized by decreased immune activation and reconstitution of naive T cells, likely of thymic origin.
- TREC levels serve as a valuable indicator of immune reconstitution in pediatric HIV patients on HAART.
Abstract:
The objective of this study was to monitor the changes in the immune system of HIV-infected children with moderate or severe immunodeficiency after highly active antiretroviral therapy (HAART), comprising a follow-up study in 14 HIV-infected children on HAART at two time points separated approximately by 11.8 +/- 0.4 (9.9; 15.4) months. HIV-infected children had significantly lower TREC levels than the control group, but 1 year after HAART the levels increased significantly (P < 0.05). In contrast, viral load (VL) did not change significantly. A positive correlation between T cell receptor excision circle (TREC) levels and both CD4(+) T cell absolute counts (r = 0.558; P = 0.05) and percentages (r = 0.625; P = 0.030) was found. During follow-up on HAART, the percentages and absolute counts of naive CD4(+) and CD8(+) T cell subsets were increased significantly (P < 0.05). CD4(+) CD45RA(hi+) CD62L(+), CD4(+) CD45RA(+) and CD4(+) CD38(+) percentages, and the CD8(+) CD45RA(hi+) CD62L(+) counts reached similar values to the control group. Also, CD8(+) CD45RO(+) CD38(+) and CD8(+) CD45RO(+) percentages, and CD8(+) CD45RO(+) CD38(+) absolute counts (P < 0.05) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (P < 0.001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG(1) and IgG(3) plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin.
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