Impact of highly active antiretroviral therapy initiation on CD4R T-cell repopulation in duodenal and rectal mucosa

Timothy L. Hayes, David Asmuth, J. William Critchfield, Thomas H. Knight, Bridget E. McLaughlin, Tammy Yotter, Delandy H. McConnell, Juan Carlos Garcia, Richard B Pollard, Barbara Shacklett

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: The objective of this study was to assess the effects of HAART initiation on CD4 T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa. Design: The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4 T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied. Methods: We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4-9 months post-HAART initiation. We examined CD4 T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4 T-cell phenotype, immune activation marker expression and HIV-specific CD8 T-cell responses in blood and rectal mucosa. Results: CD4 T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4-9 months of HAART (P1/40.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8 T-cell responses in blood and rectal mucosa declined following HAART initiation (P1/40.0015, 0.021). CD8 T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8 T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4 and CD8 T cells decreased. Conclusion: Within the first months of HAART, limited CD4 T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4 T-cell reconstitution.

Original languageEnglish (US)
Pages (from-to)867-877
Number of pages11
JournalAIDS
Volume27
Issue number6
DOIs
StatePublished - Mar 27 2013

Fingerprint

Highly Active Antiretroviral Therapy
Mucous Membrane
T-Lymphocytes
HIV
Gastrointestinal Tract
Biopsy
Death Domain Receptors
HLA-DR Antigens
Intestinal Mucosa
Duodenum
Rectum
Biomarkers

Keywords

  • Gut
  • HAART
  • HIV
  • Immune activation
  • Mucosa
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Impact of highly active antiretroviral therapy initiation on CD4R T-cell repopulation in duodenal and rectal mucosa. / Hayes, Timothy L.; Asmuth, David; Critchfield, J. William; Knight, Thomas H.; McLaughlin, Bridget E.; Yotter, Tammy; McConnell, Delandy H.; Garcia, Juan Carlos; Pollard, Richard B; Shacklett, Barbara.

In: AIDS, Vol. 27, No. 6, 27.03.2013, p. 867-877.

Research output: Contribution to journalArticle

Hayes, Timothy L. ; Asmuth, David ; Critchfield, J. William ; Knight, Thomas H. ; McLaughlin, Bridget E. ; Yotter, Tammy ; McConnell, Delandy H. ; Garcia, Juan Carlos ; Pollard, Richard B ; Shacklett, Barbara. / Impact of highly active antiretroviral therapy initiation on CD4R T-cell repopulation in duodenal and rectal mucosa. In: AIDS. 2013 ; Vol. 27, No. 6. pp. 867-877.
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T1 - Impact of highly active antiretroviral therapy initiation on CD4R T-cell repopulation in duodenal and rectal mucosa

AU - Hayes, Timothy L.

AU - Asmuth, David

AU - Critchfield, J. William

AU - Knight, Thomas H.

AU - McLaughlin, Bridget E.

AU - Yotter, Tammy

AU - McConnell, Delandy H.

AU - Garcia, Juan Carlos

AU - Pollard, Richard B

AU - Shacklett, Barbara

PY - 2013/3/27

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N2 - Objective: The objective of this study was to assess the effects of HAART initiation on CD4 T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa. Design: The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4 T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied. Methods: We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4-9 months post-HAART initiation. We examined CD4 T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4 T-cell phenotype, immune activation marker expression and HIV-specific CD8 T-cell responses in blood and rectal mucosa. Results: CD4 T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4-9 months of HAART (P1/40.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8 T-cell responses in blood and rectal mucosa declined following HAART initiation (P1/40.0015, 0.021). CD8 T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8 T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4 and CD8 T cells decreased. Conclusion: Within the first months of HAART, limited CD4 T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4 T-cell reconstitution.

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KW - Gut

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KW - HIV

KW - Immune activation

KW - Mucosa

KW - T cells

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