title: Immune reconstitution in the sigmoid colon after long-term HIV therapy.
abstract: Early and profound CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) may drive Human Immunodeficiency Virus (HIV) immunopathogenesis, and GALT immune reconstitution on highly active antiretroviral therapy (HAART) may be suboptimal. Blood and sigmoid colon biopsies were collected from HAART-treated individuals with undetectable blood HIV RNA for > or =4 years and from uninfected controls. HIV proviral levels and T-cell phenotype/function were examined in both compartments. CD4+ T-cell reconstitution in the sigmoid, including CD4+ T cells expressing CCR5, exceeded that in blood and did not differ from uninfected controls. Sigmoid HIV proviral load was not correlated with CD4+ reconsitution, but was correlated with the degree of mucosal CD8+ T-cell immune activation. Colonic Gag-specific T-cell responses were common, but were not associated with proviral load or immune activation. In this select study population, long-term HAART was associated with complete CD4+ T-cell reconstitution in sigmoid colon. However, colonic immune activation may drive ongoing HIV replication.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada. prameet.sheth@utoronto.ca
authors.forename: P M
authors.initials: PM
authors.lastname: Sheth
authors.forename: D
authors.initials: D
authors.lastname: Chege
authors.forename: L Y Y
authors.initials: LY
authors.lastname: Shin
authors.forename: S
authors.initials: S
authors.lastname: Huibner
authors.forename: F-Y
authors.initials: FY
authors.lastname: Yue
authors.forename: M
authors.initials: M
authors.lastname: Loutfy
authors.forename: R
authors.initials: R
authors.lastname: Halpenny
authors.forename: D
authors.initials: D
authors.lastname: Persad
authors.forename: C
authors.initials: C
authors.lastname: Kovacs
authors.forename: T-W
authors.initials: TW
authors.lastname: Chun
authors.forename: G
authors.initials: G
authors.lastname: Kandel
authors.forename: M
authors.initials: M
authors.lastname: Ostrowski
authors.forename: R
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D012809:Colon, Sigmoid / Q000166:cytology / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D015683:Gene Products, gag