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

Clin Infect Dis. 2012 Jul;55(2):291-300. doi: 10.1093/cid/cis383. Epub 2012 May 1.


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.

Clinical trials registration: NCT0047732.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Antiretroviral Therapy, Highly Active / methods*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects
  • Interleukin-7 / administration & dosage*
  • Interleukin-7 / adverse effects
  • Placebos / administration & dosage
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Treatment Outcome


  • Anti-HIV Agents
  • IL7 protein, human
  • Immunologic Factors
  • Interleukin-7
  • Placebos
  • Recombinant Proteins