Impaired CD4+ T-cell restoration in the small versus large intestine of HIV-1-positive South Africans receiving combination antiretroviral therapy

Edana Cassol, Susan Malfeld, Phetole Mahasha, Robert Bond, Tomas Slavik, Chris Seebregts, Guido Poli, Sharon Cassol, Schalk W. Van Der Merwe, Theresa Rossouw

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Human immunodeficiency virus type 1 (HIV-1) infection is associated with a massive depletion of intestinal CD4+ T cells that is only partially reversed by combination antiretroviral therapy (cART). Here, we assessed the ability of nucleoside reverse-transcriptase inhibitor/ nonnucleoside reverse-transcriptase inhibitor treatment to restore the CD4 + T-cell populations in the intestine of South African patients with AIDS.Methods. Thirty-eight patients with advanced HIV-1 infection who had chronic diarrhea (duration, >4 weeks) and/or unintentional weight loss (>10% decrease from baseline) of uncertain etiology were enrolled. Blood specimens were collected monthly, and gastrointestinal tract biopsy specimens were collected before cART initiation (from the duodenum, jejunum, ileum, and colon), 3 months after cART initiation (from the duodenum), and 6 months after cART initiation (from the duodenum and colon). CD4+, CD8+, and CD38+CD8+ T cells were quantified by flow cytometry and immunohistochemistry analyses, and the HIV-1 RNA load was determined by the Nuclisens assay.Results. CD4+ T-cell and HIV-1 RNA levels were significantly lower, whereas CD8+ T-cell levels, including activated CD38+CD8+ T cell levels, were higher in the duodenum and jejunum, compared with the colon. After 6 months of cART, a significant but incomplete recovery of CD4+ T cells was detected in the colon and peripheral blood but not in the duodenum. Failed restoration of the CD4 + T-cell count in the duodenum was associated with nonspecific enteritis and CD8+ T-cell activation.Conclusions. Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4+ T-cell recovery and improve therapeutic outcomes.

Original languageEnglish
Pages (from-to)1113-1122
Number of pages10
JournalJournal of Infectious Diseases
Volume208
Issue number7
DOIs
Publication statusPublished - Oct 1 2013

Keywords

  • Africa
  • antiretroviral therapy
  • CD4 reconstitution
  • HIV-1
  • immune activation
  • intestine

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Medicine(all)

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