A randomized controlled trial of palifermin (recombinant human keratinocyte growth factor) for the treatment of inadequate CD4+ T-lymphocyte recovery in patients with HIV-1 infection on antiretroviral therapy

J Acquir Immune Defic Syndr. 2014 Aug 1;66(4):399-406. doi: 10.1097/QAI.0000000000000195.

Abstract

Background: Poor CD4 lymphocyte recovery on antiretroviral therapy (ART) is associated with reduced function of the thymus. Palifermin (keratinocyte growth factor), by providing support to the thymic epithelium, promotes lymphopoiesis in animal models of bone marrow transplantation and graft-versus-host disease.

Methods: In AIDS Clinical Trials Group A5212, a randomized, double-blind, placebo-controlled study, 99 HIV-infected patients on ART with plasma HIV-1 RNA levels ≤200 copies per milliliter for ≥6 months and CD4 lymphocyte counts <200 cells per cubic milliliter were randomized 1:1:1:1 to receive once daily intravenous administration of placebo or 20, 40, or 60 μg/kg of palifermin on 3 consecutive days.

Results: The median change in the CD4 T-cell count from baseline to week 12 was not significantly different between the placebo arm [15 (-16, 23) cells/mm] and the 20-μg/kg dose [11 (2, 32) cells/mm], the 40-μg/kg dose [12 (-2, 25) cells/mm], or the 60-μg/kg dose arm [8 (-13, 35) cells/mm] of palifermin. No significant changes were observed in thymus size or in the number of naive T cells or recent thymic emigrants.

Conclusions: Palifermin in the doses studied was not effective in improving thymic function and did not raise CD4 lymphocyte counts in HIV-infected patients with low CD4 cell counts despite virologically effective ART.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fibroblast Growth Factor 7 / administration & dosage
  • Fibroblast Growth Factor 7 / pharmacology*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1*
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral
  • Recombinant Proteins
  • Thymus Gland / drug effects
  • Viral Load

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Recombinant Proteins
  • Fibroblast Growth Factor 7

Grants and funding