The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected participants.
PLoS One
; 5(8): e11937, 2010 Aug 03.
Article
em En
| MEDLINE
| ID: mdl-20689824
ABSTRACT
BACKGROUND:
The pathogenesis of immunodeficiency due to human immunodeficiency virus (HIV)-1 is incompletely understood, but immune activation is believed to play a central role. Immunomodulatory agents that decrease immune activation may be useful in the treatment of HIV-1 infection.METHODOLOGY:
A randomized, double blind, placebo-controlled pilot study of leflunomide for 28 days was performed in participants with HIV-1 infection who were not receiving antiretroviral therapy. Participants randomized to leflunomide were subsequently treated with cholestyramine until leflunomide levels were below detection limit.FINDINGS:
Treatment with leflunomide was well tolerated with mostly low-grade adverse events. Leflunomide administration reduced cycling of CD4 T cells (by ex vivo bromodeoxyuridine uptake and Ki67 expression) and decreased expression of activation markers (HLA-DR/CD38 co-expression) on CD8 T cells in peripheral blood. In addition, decreased expression of HIV-1 co-receptors was observed in both CD4 and CD8 T cells in the leflunomide group. There were no significant changes in naïve and memory T cell subsets, apoptosis of T cells or markers of microbial translocation.CONCLUSIONS:
Leflunomide was effective in reducing immune activation in the setting of chronic HIV-1 infection suggesting that targeting immune activation with immunomodulatory agents may be a feasible strategy. TRIAL REGISTRATION ClinicalTrials.gov NCT00101374.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Infecções por HIV
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HIV-1
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Fatores Imunológicos
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Isoxazóis
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article