Immune activation despite preserved CD4 T cells in perinatally HIV-infected children and adolescents
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Updated: Feb 16, 2026
Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model
Published on: July 2, 2016
Patricia Alvarez1, Mussa Mwamzuka2, Fatma Marshed2
1HIV-1 Molecular Epidemiology Laboratory, Department of Microbiology and Parasitology, Hospital Ramon y Cajal-IRYCIS and CIBERESP, Madrid, Spain.
Insights
Early antiretroviral therapy (ART) is crucial for children with HIV. Despite normal CD4 counts, untreated HIV+ children show immune activation, highlighting the need for prompt treatment to prevent long-term inflammation.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Public Health
Background:
- HIV progresses rapidly in children, with high mortality without treatment in sub-Saharan Africa.
- World Health Organization guidelines recommend universal HIV treatment, but pediatric evidence is limited.
- This study investigates immunological markers in perinatally-infected children and adolescents.
Purpose of the Study:
- To assess if CD4 cell counts reflect disease progression markers in untreated HIV+ children.
- To evaluate immune responses to antiretroviral therapy (ART) in pediatric HIV.
- To inform treatment guidelines for pediatric HIV.
Main Methods:
- Collected blood samples from HIV-negative and HIV-positive children (ages 1-19) in Kenya.
- Analyzed immune activation markers (CD38, HLA-DR, Ki67) via flow cytometry.
- Quantified plasma soluble CD14 (sCD14) using ELISA.
Main Results:
- HIV+ children with high CD4 counts had low CD4 percentages and CD4:CD8 ratios, with high immune activation.
- ART rapidly reduced T cell activation but did not normalize CD4:CD8 ratios or sCD14 levels.
- Immune activation and altered CD4 metrics occurred independently of CD4 count thresholds in untreated children.
Conclusions:
- Prompt ART initiation is vital for HIV+ children to mitigate inflammation.
- CD4 cell counts alone may not fully represent disease status in pediatric HIV.
- Current WHO guidelines for universal ART are supported by findings in pediatric populations.
Background:
HIV disease progresses more rapidly in children than adults with mortality rates exceeding 50% by 2 years of age without antiretroviral therapy (ART) in sub-Saharan Africa. Recent World Health Organization (WHO) guidelines recommend universal treatment for all living persons with HIV, yet there is limited supporting evidence in pediatric populations. The objective of this study was to determine whether CD4 cell counts reflect immunological markers associated with disease progression in ART naïve perinatally-infected HIV+ children and adolescents and their response to ART.
Methods:
PBMC and plasma samples were collected from 71 HIV negative and 132 HIV+ children (65 ART naïve and 67 on ART) between ages 1-19 years from Mombasa, Kenya. Untreated HIV+ subjects were sub-categorized by high or low CD4 T cell counts. Immune activation markers CD38, HLA-DR and Ki67 were analyzed by flow cytometry. Plasma soluble CD14 (sCD14) was quantified by ELISA.
Results:
HIV-infected children and adolescents with preserved CD4 cell counts had depleted CD4 percentages and CD4:CD8 ratios, and high immune activation levels. ART initiation rapidly and persistently reversed T cell activation, but failed to normalize CD4:CD8 ratios and plasma sCD14 levels.
Conclusions:
Diminished CD4 percentages and CD4:CD8 ratios along with profound immune activation occur independent of CD4 cell count thresholds in ART naïve HIV+ children and adolescents. Immediate ART initiation, as recommended in the most recent WHO guidelines may protect them from pathologic sequelae associated with persistent inflammation.
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