title: NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption.
abstract: Long-term side effects may represent a relevant burden of antiretroviral treatment (ART) in HIV-infected patients with good CD4 immune reconstitution over extended time spans. CD4-guided treatment interruption (TI) has been evaluated to address this point and may result in a wide spectrum of time off ART in different patient cohorts. We studied whether differences in innate immune responses, in particular NK cells, are associated to patterns of longer (LoTI) or a shorter (ShTI) TI. Clinical cohort parameters were analyzed on a group of patients widely diverging for TI duration (<9 versus >18 months) on samples before TI, including NK-cell analysis and function by natural cytotoxicity receptor (NCR)-triggered γ-IFN production. Although persistently reduced NCR expression (NKp30) and function were observed in both LoTI and ShTI patients on ART compared with healthy donors, relevant differences were observed at baseline TI in those patients who subsequently developed LoTI course. Lower expression of NKG2D and NKp46 on NK cells. This also translates in reduced γ-IFN production in redirected functional assays. Thus, differences in innate immune balance exist during ART, may be associated to differential control of HIV infection and their understanding could explain clinical differences in individual patients that are not reflected by CD4(+) cell counts alone.
authors.affiliation: Istituto G.Gaslini, Genova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bozzano
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Linda
authors.initials: L
authors.lastname: Bertoncelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Nemes
authors.forename: Francesca
authors.initials: F
authors.lastname: Prati
authors.forename: Francesco
authors.initials: F
authors.lastname: Marras
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology; D010641:Phenotype
chemical_list: D044966:Anti-Retroviral Agents; D055627:Natural Cytotoxicity Triggering Receptor 1