title: Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results of 2 Phase II Multicenter Studies.
abstract: BACKGROUND
  Phase I/II studies in human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy have shown that a single cycle of 3 weekly subcutaneous (s/c) injections of recombinant human interleukin 7 (r-hIL-7) is safe and improves immune CD4 T-cell restoration. Herein, we report data from 2 phase II trials evaluating the effect of repeated cycles of r-hIL-7 (20 µg/kg) with the objective of restoring a sustained CD4 T-cell count >500 cells/µL.
  
  
  METHODS
  INSPIRE 2 was a single-arm trial conducted in the United States and Canada. INSPIRE 3 was a 2 arm trial with 3:1 randomization to r-hIL-7 versus control conducted in Europe and South Africa. Participants with plasma HIV RNA levels <50 copies/mL during antiretroviral therapy and with CD4 T-cell counts between 101 and 400 cells/µL were eligible. A repeat cycle was administered when CD4 T-cell counts fell to <550 cells/µL.
  
  
  RESULTS
  A total of 107 patients were treated and received 1 (n = 107), 2 (n = 74), 3 (n = 14), or 4 (n = 1) r-hIL-7 cycles during a median follow-up of 23 months. r-hIL-7 was well tolerated. Four grade 4 events were observed, including 1 case of asymptomatic alanine aminotransferase elevation. After the second cycle, anti-r-hIL-7 binding antibodies developed in 82% and 77% of patients in INSPIRE 2 and 3, respectively (neutralizing antibodies in 38% and 37%), without impact on the CD4 T-cell response. Half of the patients spent >63% of their follow-up time with a CD4 T-cell count >500 cells/µL.
  
  
  CONCLUSIONS
  Repeated cycles of r-hIL-7 were well tolerated and achieved sustained CD4 T-cell restoration to >500 cells/µL in the majority of study participants.
  
  
  BACKGROUND
  INSPIRE II: clinicaltrials.gov (NCT01190111) and INSPIRE III: EudraCT (No. 2010-019773-15) and clinicaltrials.gov (NCT01241643).
authors.affiliation: INSERM U1219, INRIA SISTM, Bordeaux University.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.affiliation: INSERM U1219, INRIA SISTM, Bordeaux University.
authors.forename: Ana
authors.initials: A
authors.lastname: Jarne
authors.affiliation: McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: University of Miami Miller School of Medicine, Florida.
authors.forename: Margaret
authors.initials: M
authors.lastname: Fischl
authors.affiliation: Clinical HIV Research Unit, Johannesburg.
authors.forename: Prudence
authors.initials: P
authors.lastname: Ive
authors.affiliation: Division of Infectious Diseases, University of Zurich, University Hospital of Zurich, Switzerland.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Speck
authors.affiliation: Institute for Infectious Diseases Lazzaro Spallanzani, Rome.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: D'Offizi
authors.affiliation: Infectious and Tropical Diseases Unit, Brescia.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Casari
authors.affiliation: INSERM U1219, INRIA SISTM, Bordeaux University.
authors.forename: Daniel
authors.initials: D
authors.lastname: Commenges
authors.affiliation: JOSHA Research, Bloemfontein, South Africa.
authors.forename: Sharne
authors.initials: S
authors.lastname: Foulkes
authors.affiliation: Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Maryland.
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
authors.affiliation: INSERM/ANRS, Paris.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Croughs
authors.affiliation: INSERM/ANRS, Paris.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Tambussi
authors.affiliation: INSERM U955, Université Paris Est, Faculté de Médecine, Créteil, Vaccine Research Institute Créteil, AP-HP, Hôpital H. Mondor-A. Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D015851:Interleukin-7 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D015851:Interleukin-7; D011994:Recombinant Proteins
keywords: CD4; HIV; T-cell recovery; immune restoration; interleukin-7