title: Impaired CD4+ T-cell restoration in the small versus large intestine of HIV-1-positive South Africans receiving combination antiretroviral therapy.
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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston MA 02215, USA. edana_cassol@dfci.harvard.edu
authors.forename: Edana
authors.initials: E
authors.lastname: Cassol
authors.forename: Susan
authors.initials: S
authors.lastname: Malfeld
authors.forename: Phetole
authors.initials: P
authors.lastname: Mahasha
authors.forename: Robert
authors.initials: R
authors.lastname: Bond
authors.forename: Tomas
authors.initials: T
authors.lastname: Slavik
authors.forename: Chris
authors.initials: C
authors.lastname: Seebregts
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
authors.forename: Sharon
authors.initials: S
authors.lastname: Cassol
authors.forename: Schalk W
authors.initials: SW
authors.lastname: van der Merwe
authors.forename: Theresa
authors.initials: T
authors.lastname: Rossouw
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D007420:Intestine, Large / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013019:South Africa; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents
keywords: Africa; CD4 reconstitution; HIV-1; antiretroviral therapy; immune activation; intestine