Changes in cellular immune activation and memory T-cell subsets in HIV-infected Zambian children receiving HAART

Kaitlin Rainwater-Lovett1, Hope Nkamba, Mwangelwa Mubiana-Mbewe

  • 1*Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; †Virology Laboratory, University Teaching Hospital, Lusaka, Zambia; ‡Center for Infectious Disease Research-Zambia, Lusaka, Zambia; §Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL; and ‖Department of W. Harry Feinstone Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Dr Kaitlin Rainwater-Lovett is now with Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD; Carolyn B. Moore is now with Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, NC).

Insights

Highly active antiretroviral therapy (HAART) in Zambian children with HIV reduced immune activation and effector memory CD4+ T cells. However, effector memory T cells remained elevated, suggesting ongoing immune system changes.

Area of Science:

  • Immunology
  • Pediatric Infectious Diseases
  • HIV/AIDS Research

Background:

  • Sub-Saharan African children face high pathogen exposure, potentially increasing immune activation and memory T cells.
  • Understanding T-cell subset dynamics during highly active antiretroviral therapy (HAART) is crucial for immune restoration in young children with HIV in this region.

Purpose of the Study:

  • To characterize changes in CD4+ and CD8+ T-cell subsets in HIV-infected Zambian children receiving HAART.
  • To assess the impact of HAART on immune activation and T-cell memory populations.

Main Methods:

  • Flow cytometry was used to measure T-cell subsets in 157 HIV-infected children before and during HAART (up to 30 months).
  • A control group of 34 children was included for comparison.
  • Longitudinal follow-up data were collected at 3-month intervals.

Main Results:

  • Before HAART, HIV-infected children exhibited higher immune activation and effector memory (EM) T cells, with lower naive T cells and IL-7Rα-expressing CD8+ T cells compared to controls.
  • HAART led to a decline in immune activation and EM CD4+ T cells within 6 months.
  • Persistently elevated EM CD4+ T cells and effector CD8+ T cells were observed up to 30 months, while IL-7Rα-expressing CD8+ T cells increased, indicating potential memory capacity expansion.

Conclusions:

  • HAART effectively reduces immune activation and EM CD4+ T cells, while promoting naive T-cell and IL-7Rα-expressing CD8+ T-cell reconstitution.
  • Sustained high levels of EM CD4+ T cells suggest persistent alterations in T-cell subset composition in HIV-infected children despite HAART.
Abstract

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