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, M. 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

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

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ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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Lévy, Y., Sereti, I., Tambussi, G., Routy, J. P., Lelièvre, J. D., Delfraissy, J. F., Molina, J. M., Fischl, M., 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. (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, 55(2), 291-300. https://doi.org/10.1093/cid/cis383