title: Early initiation of combined antiretroviral therapy preserves immune function in the gut of HIV-infected patients.
abstract: Massive loss of lamina propria CD4(+) T cells, changes in the lymphatic architecture, and altered intestinal epithelial barrier leading to microbial translocation are the common features of HIV-1 infection and are not fully restored under combined antiretroviral therapy (cART). To better understand determinants of gut mucosal restoration, we have performed phenotypic and gene expression analyses of the gut from HIV-infected patients, naive or treated with cART initiated either at the early phase of the primary infection or later during the chronic phase. We found a depletion of T helper type 22 (Th22) and interleukin-17-producing cells in naive patients. These populations, except Th22 cells, were not restored under cART. Regulatory T cells/Th17 ratio was significantly increased in HIV-infected patients and was inversely correlated to the restoration of CD4(+) T cells but not to gut HIV DNA levels. Gene profile analysis of gut mucosal distinguished two groups of patients, which fitted with the timing of cART initiation. In their majority early, but not later treated patients, exhibited conserved intestinal lymphoid structure, epithelial barrier integrity and dendritic cell maturation pathways. Our data demonstrate that early initiation of cART helps to preserve and/or restore lymphoid gut mucosal homeostasis and provide a rationale for initiating cART during the acute phase of HIV infection.
authors.affiliation: 1] INSERM U955, Team 16, Créteil, France [2] Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France [3] Université Paris Est Créteil, Faculté de Médecine, Créteil, France.
authors.forename: A
authors.initials: A
authors.lastname: Kök
authors.affiliation: Service des Maladies Infectieuses et Tropicales, CHR d'Orléans-La Source, Orléans, France.
authors.forename: L
authors.initials: L
authors.lastname: Hocqueloux
authors.affiliation: 1] INSERM U955, Team 16, Créteil, France [2] Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France.
authors.forename: H
authors.initials: H
authors.lastname: Hocini
authors.affiliation: INSERM U955, Team 16, Créteil, France.
authors.forename: M
authors.initials: M
authors.lastname: Carrière
authors.affiliation: Service d'Hépato-Gastro-Entérologie, CHR d'Orléans-La Source, Orléans, France.
authors.forename: L
authors.initials: L
authors.lastname: Lefrou
authors.affiliation: 1] INSERM U955, Team 16, Créteil, France [2] Plateforme de Cytométrie en flux, IMRB, UFR de Médecine, Créteil, France.
authors.forename: A
authors.initials: A
authors.lastname: Guguin
authors.affiliation: 1] INSERM U955, Team 16, Créteil, France [2] Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Tisserand
authors.affiliation: 1] Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France [2] INSERM U897 - INRIA SISTM - Univ. Bordeaux Segalen ISPED, Bordeaux, France.
authors.forename: H
authors.initials: H
authors.lastname: Bonnabau
authors.affiliation: AP-HP, CHU Necker-Enfants Malades, Laboratoire de Virologie, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Avettand-Fenoel
authors.affiliation: Service des Maladies Infectieuses et Tropicales, CHR d'Orléans-La Source, Orléans, France.
authors.forename: T
authors.initials: T
authors.lastname: Prazuck
authors.affiliation: Assistance publique -Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil, Val-de Marne, France.
authors.forename: S
authors.initials: S
authors.lastname: Katsahian
authors.affiliation: 1] Université Paris Est Créteil, Faculté de Médecine, Créteil, France [2] INSERM U955, Team 9, Créteil, France [3] Département de Pathologie, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Gaulard
authors.affiliation: 1] Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France [2] INSERM U897 - INRIA SISTM - Univ. Bordeaux Segalen ISPED, Bordeaux, France.
authors.forename: R
authors.initials: R
authors.lastname: Thiébaut
authors.affiliation: 1] INSERM U955, Team 16, Créteil, France [2] Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France [3] Université Paris Est Créteil, Faculté de Médecine, Créteil, France [4] Service d'Immunologie Clinique, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Lévy
authors.affiliation: 1] INSERM U955, Team 16, Créteil, France [2] Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France [3] Université Paris Est Créteil, Faculté de Médecine, Créteil, France [4] Service d'Immunologie Biologique, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France.
authors.forename: S
authors.initials: S
authors.lastname: Hüe
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004279:DNA, Viral / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D007378:Interleukins / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D016896:Treatment Outcome; D000097043:Interleukin-22
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D007378:Interleukins; D000097043:Interleukin-22