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.

TitleA 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.
Publication TypeJournal Article
Year of Publication2014
AuthorsJacobson JM, Wang H, Bordi R, Zheng L, Gross BH, Landay AL, Spritzler J, Routy J-P, Benson C, Aberg J, Tebas P, Haas DW, Tiu J, Coughlin K, Purdue L, Sekaly R-P
Corporate AuthorsAIDS Clinical Trials Group(ACTG) A5212 Protocol Team
JournalJ Acquir Immune Defic Syndr
Volume66
Issue4
Pagination399-406
Date Published2014 Aug 1
ISSN1944-7884
KeywordsAdult, Anti-HIV Agents, CD4 Lymphocyte Count, Dose-Response Relationship, Drug, Double-Blind Method, Female, Fibroblast Growth Factor 7, HIV Infections, HIV-1, Humans, Male, Middle Aged, Recombinant Proteins, RNA, Viral, Thymus Gland, Viral Load
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.

DOI10.1097/QAI.0000000000000195
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID24815851
PubMed Central IDPMC4216663
Grant List1U01AI69467 / AI / NIAID NIH HHS / United States
1U01AL069418-01 / / PHS HHS / United States
5 UM1 AI069477 / AI / NIAID NIH HHS / United States
5-U01 AI069423-03 / AI / NIAID NIH HHS / United States
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5U01A1069472 / / PHS HHS / United States
5UM1-AI069484-07 / AI / NIAID NIH HHS / United States
5UM1AI069470-07 / AI / NIAID NIH HHS / United States
A1 069424 / / PHS HHS / United States
AI-069439 / AI / NIAID NIH HHS / United States
AI050410 / AI / NIAID NIH HHS / United States
AI069428 / AI / NIAID NIH HHS / United States
AI069434 / AI / NIAID NIH HHS / United States
AI069495 / AI / NIAID NIH HHS / United States
AI069556 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
AI69501 / AI / NIAID NIH HHS / United States
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P30 AI050409 / AI / NIAID NIH HHS / United States
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RR 025747 / RR / NCRR NIH HHS / United States
U01 AI069474 / AI / NIAID NIH HHS / United States
U01A1069447 / / PHS HHS / United States
U01AI069511-02 / AI / NIAID NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UL1 TR000042 / TR / NCATS NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
UL1TR000454 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
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UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069428 / AI / NIAID NIH HHS / United States
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UM1 AI069434 / AI / NIAID NIH HHS / United States
UM1 AI069439 / AI / NIAID NIH HHS / United States
UM1 AI069447 / AI / NIAID NIH HHS / United States
UM1 AI069467 / AI / NIAID NIH HHS / United States
UM1 AI069470 / AI / NIAID NIH HHS / United States
UM1 AI069472 / AI / NIAID NIH HHS / United States
UM1 AI069474 / AI / NIAID NIH HHS / United States
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UM1 AI069484 / AI / NIAID NIH HHS / United States
UM1 AI069495 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States
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UM1 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI069556 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States