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

Rodolphe Thiebaut, Ana Jarne, Jean Pierre Routy, Irini Sereti, Margaret A Fischl, Prudence Ive, Roberto F. Speck, Gianpiero D'Offizi, Salvatore Casari, Daniel Commenges, Sharne Foulkes, Ven Natarajan, Therèse Croughs, Jean François Delfraissy, Guiseppe Tambussi, Yves Levy, Michael M. Lederman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1178-1185
Number of pages8
JournalClinical Infectious Diseases
Volume62
Issue number9
DOIs
StatePublished - May 1 2016

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Interleukin-7
Multicenter Studies
HIV
T-Lymphocytes
CD4 Lymphocyte Count
Subcutaneous Injections
Therapeutics
Random Allocation
South Africa
Canada
RNA

Keywords

  • CD4
  • HIV
  • immune restoration
  • Interleukin-7
  • T-cell recovery

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

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. / Thiebaut, Rodolphe; Jarne, Ana; Routy, Jean Pierre; Sereti, Irini; Fischl, Margaret A; Ive, Prudence; Speck, Roberto F.; D'Offizi, Gianpiero; Casari, Salvatore; Commenges, Daniel; Foulkes, Sharne; Natarajan, Ven; Croughs, Therèse; Delfraissy, Jean François; Tambussi, Guiseppe; Levy, Yves; Lederman, Michael M.

In: Clinical Infectious Diseases, Vol. 62, No. 9, 01.05.2016, p. 1178-1185.

Research output: Contribution to journalArticle

Thiebaut, R, Jarne, A, Routy, JP, Sereti, I, Fischl, MA, Ive, P, Speck, RF, D'Offizi, G, Casari, S, Commenges, D, Foulkes, S, Natarajan, V, Croughs, T, Delfraissy, JF, Tambussi, G, Levy, Y & Lederman, MM 2016, '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', Clinical Infectious Diseases, vol. 62, no. 9, pp. 1178-1185. https://doi.org/10.1093/cid/ciw065
Thiebaut, Rodolphe ; Jarne, Ana ; Routy, Jean Pierre ; Sereti, Irini ; Fischl, Margaret A ; Ive, Prudence ; Speck, Roberto F. ; D'Offizi, Gianpiero ; Casari, Salvatore ; Commenges, Daniel ; Foulkes, Sharne ; Natarajan, Ven ; Croughs, Therèse ; Delfraissy, Jean François ; Tambussi, Guiseppe ; Levy, Yves ; Lederman, Michael M. / 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. In: Clinical Infectious Diseases. 2016 ; Vol. 62, No. 9. pp. 1178-1185.
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abstract = "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.",
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AU - Jarne, Ana

AU - Routy, Jean Pierre

AU - Sereti, Irini

AU - Fischl, Margaret A

AU - Ive, Prudence

AU - Speck, Roberto F.

AU - D'Offizi, Gianpiero

AU - Casari, Salvatore

AU - Commenges, Daniel

AU - Foulkes, Sharne

AU - Natarajan, Ven

AU - Croughs, Therèse

AU - Delfraissy, Jean François

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N2 - 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.

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