title: Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells.
abstract: CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.
authors.affiliation: Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark; Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark.
authors.forename: Sanne Skov
authors.initials: SS
authors.lastname: Jensen
authors.affiliation: Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark; Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Fomsgaard
authors.affiliation: Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Tine Kochendorf
authors.initials: TK
authors.lastname: Larsen
authors.affiliation: Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Jeanette Linnea
authors.initials: JL
authors.lastname: Tingstedt
authors.affiliation: Viro-immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.affiliation: Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Karlsson
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents