title: Impact of highly active antiretroviral therapy initiation on CD4(+) T-cell repopulation in duodenal and rectal mucosa.
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.
  
  
  METHODS
  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 (P = 0.02, 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 (P = 0.0015, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDepartment of Medical Microbiology and Immunology bDivision of Infectious Diseases cDivision of Gastroenterology, Department of Internal Medicine, School of Medicine, University of California, Davis, California, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Hayes
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.forename: J William
authors.initials: JW
authors.lastname: Critchfield
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Knight
authors.forename: Bridget E
authors.initials: BE
authors.lastname: McLaughlin
authors.forename: Tammy
authors.initials: T
authors.lastname: Yotter
authors.forename: Delandy H
authors.initials: DH
authors.lastname: McConnell
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Garcia
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Shacklett
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001706:Biopsy; D001769:Blood / Q000276:immunology; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004386:Duodenum / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D012007:Rectum / Q000276:immunology*
chemical_list: D018106:CD28 Antigens