title: Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study.
abstract: BACKGROUND
  The immune deficiency of human immunodeficiency virus (HIV) infection is not fully corrected with ARV therapy. Interleukin-7 (IL-7) can boost CD4 T-cell counts, but optimal dosing and mechanisms of cellular increases need to be defined.
  
  
  METHODS
  We performed a randomized placebo-controlled dose escalation (10, 20 and 30 µg/kg) trial of 3 weekly doses of recombinant human IL-7 (rhIL-7) in ARV-treated HIV-infected persons with CD4 T-cell counts between 101 and 400 cells/µL and plasma HIV levels <50 copies/mL. Toxicity, activity and the impact of rhIL-7 on immune reconstitution were monitored.
  
  
  RESULTS
  Doses of rhIL-7 up to 20 µg/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/µL at 12 weeks) and durable (up to 1 year). Increased cell cycling and transient increased bcl-2 expression were noted. Expanded cells did not have the characteristics of regulatory or activated T cells. Transient low-level HIV viremia was seen in 6 of 26 treated patients; modest increases in total levels of intracellular HIV DNA were proportional to CD4 T-cell expansions. IL-7 seemed to increase thymic output and tended to improve the T-cell receptor (TCR) repertoire in persons with low TCR diversity.
  
  
  CONCLUSIONS
  Three weekly doses of rhIL-7 at 20 µg/kg are well tolerated and lead to a dose-dependent CD4 T-cell increase and the broadening of TCR diversity in some subjects. These data suggest that this rhIL-7 dose could be advanced in future rhIL-7 clinical studies.
  
  
  BACKGROUND
  NCT0047732.
authors.affiliation: Inserm, U955, France. yves.levy@hmn.aphp.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Lévy
authors.forename: I
authors.initials: I
authors.lastname: Sereti
authors.forename: G
authors.initials: G
authors.lastname: Tambussi
authors.forename: J P
authors.initials: JP
authors.lastname: Routy
authors.forename: J D
authors.initials: JD
authors.lastname: Lelièvre
authors.forename: J F
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: J M
authors.initials: JM
authors.lastname: Molina
authors.forename: M
authors.initials: M
authors.lastname: Fischl
authors.forename: C
authors.initials: C
authors.lastname: Goujard
authors.forename: B
authors.initials: B
authors.lastname: Rodriguez
authors.forename: C
authors.initials: C
authors.lastname: Rouzioux
authors.forename: V
authors.initials: V
authors.lastname: Avettand-Fenoël
authors.forename: T
authors.initials: T
authors.lastname: Croughs
authors.forename: S
authors.initials: S
authors.lastname: Beq
authors.forename: M
authors.initials: M
authors.lastname: Morre
authors.forename: J F
authors.initials: JF
authors.lastname: Poulin
authors.forename: R P
authors.initials: RP
authors.lastname: Sekaly
authors.forename: R
authors.initials: R
authors.lastname: Thiebaut
authors.forename: M M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; C508605:IL7 protein, human; D007155:Immunologic Factors; D015851:Interleukin-7; D010919:Placebos; D011994:Recombinant Proteins