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

Y. Lévy, I. Sereti, G. Tambussi, J. P. Routy, J. D. Lelièvre, J. F. Delfraissy, J. M. Molina, Margaret A Fischl, C. Goujard, B. Rodriguez, C. Rouzioux, V. Avettand-Fenoël, T. Croughs, S. Beq, M. Morre, J. F. Poulin, R. P. Sekaly, R. Thiebaut, M. M. Lederman

Research output: Contribution to journalArticle

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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 g/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/L 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 g/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/L 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 g/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. Clinical Trials Registration NCT0047732.

Original languageEnglish
Pages (from-to)291-300
Number of pages10
JournalClinical Infectious Diseases
Volume55
Issue number2
DOIs
StatePublished - Jul 15 2012

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Interleukin-7
Multicenter Studies
Placebos
HIV
T-Lymphocytes
T-Cell Antigen Receptor
Therapeutics
CD4 Lymphocyte Count
Viremia
Virus Diseases
Plasma Cells
Clinical Trials
DNA

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

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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. / Lévy, Y.; Sereti, I.; Tambussi, G.; Routy, J. P.; Lelièvre, J. D.; Delfraissy, J. F.; Molina, J. M.; Fischl, Margaret A; Goujard, C.; Rodriguez, B.; Rouzioux, C.; Avettand-Fenoël, V.; Croughs, T.; Beq, S.; Morre, M.; Poulin, J. F.; Sekaly, R. P.; Thiebaut, R.; Lederman, M. M.

In: Clinical Infectious Diseases, Vol. 55, No. 2, 15.07.2012, p. 291-300.

Research output: Contribution to journalArticle

Lévy, Y, Sereti, I, Tambussi, G, Routy, JP, Lelièvre, JD, Delfraissy, JF, Molina, JM, Fischl, MA, Goujard, C, Rodriguez, B, Rouzioux, C, Avettand-Fenoël, V, Croughs, T, Beq, S, Morre, M, Poulin, JF, Sekaly, RP, Thiebaut, R & Lederman, MM 2012, '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', Clinical Infectious Diseases, vol. 55, no. 2, pp. 291-300. https://doi.org/10.1093/cid/cis383
Lévy, Y. ; Sereti, I. ; Tambussi, G. ; Routy, J. P. ; Lelièvre, J. D. ; Delfraissy, J. F. ; Molina, J. M. ; Fischl, Margaret A ; Goujard, C. ; Rodriguez, B. ; Rouzioux, C. ; Avettand-Fenoël, V. ; Croughs, T. ; Beq, S. ; Morre, M. ; Poulin, J. F. ; Sekaly, R. P. ; Thiebaut, R. ; Lederman, M. M. / 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. In: Clinical Infectious Diseases. 2012 ; Vol. 55, No. 2. pp. 291-300.
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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 g/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/L 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 g/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/L 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 g/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. Clinical Trials Registration NCT0047732.",
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T2 - Results of a phase I/IIa randomized, placebo-controlled, multicenter study

AU - Lévy, Y.

AU - Sereti, I.

AU - Tambussi, G.

AU - Routy, J. P.

AU - Lelièvre, J. D.

AU - Delfraissy, J. F.

AU - Molina, J. M.

AU - Fischl, Margaret A

AU - Goujard, C.

AU - Rodriguez, B.

AU - Rouzioux, C.

AU - Avettand-Fenoël, V.

AU - Croughs, T.

AU - Beq, S.

AU - Morre, M.

AU - Poulin, J. F.

AU - Sekaly, R. P.

AU - Thiebaut, R.

AU - Lederman, M. M.

PY - 2012/7/15

Y1 - 2012/7/15

N2 - 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 g/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/L 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 g/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/L 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 g/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. Clinical Trials Registration NCT0047732.

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