title: CD4+ T-cell differentiation, regulatory T cells and gag-specific T lymphocytes are unaffected by CD4-guided treatment interruption and therapy resumption.
abstract: OBJECTIVE
  Despite limiting exposure to antiretroviral drugs, structured treatment interruptions can influence multiple aspects of T-cell immunity, particularly those regarding CD4(+) T lymphocytes. We evaluated the impact of CD4-guided treatment interruption (CD4-GTI) and treatment resumption on regulatory T cells (Tregs), T-lymphocyte activation, differentiation and polyfunctional gag-specific response.
  
  
  METHODS
  Patients were analyzed just prior to treatment interruption, at 2 and 6 months after treatment interruption, just prior to treatment resumption and at 2 and 6 months after treatment resumption. Thawed peripheral blood mononuclear cells were stained immediately for phenotype analysis or stimulated with HIV-gag peptides and analyzed by polychromatic flow cytometry.
  
  
  RESULTS
  Treatment interruption resulted in a CD4(+) cell count decrease and plasma viral load (pVL) increase, but did not preclude a good immune reconstitution and a complete suppression of pVL after treatment resumption. Treatment interruption did not influence CD4(+) T-cell differentiation and Treg subsets. During treatment interruption, gag-specific CD4(+) T cells were not lost, although the frequency of HIV-specific CD8(+) cells increased. Most gag-specific CD4(+) T cells were potentially cytotoxic (CD107a(+)) and were not influenced by pVL or by HAART. Most helper (CD154(+)) gag-specific CD4(+) T lymphocytes did not produce interferon-γ or interleukin-2.
  
  
  CONCLUSIONS
  CD4-GTI did not cause depletion of memory cells, Tregs or HIV-specific CD4(+) cells and, on the contrary, could induce HIV-specific responses. If guided by CD4(+) T-cell count, treatment interruption does not provoke irreversible immune damages.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nemes
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Linda
authors.initials: L
authors.lastname: Bertoncelli
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.forename: Serena
authors.initials: S
authors.lastname: Manzini
authors.forename: Francesca
authors.initials: F
authors.lastname: Prati
authors.forename: Lisa
authors.initials: L
authors.lastname: Manzini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D019562:Viral Load