Quantifying and predicting the effect of exogenous interleukin-7 on CD4+ T cells in HIV-1 infection.
Exogenous Interleukin-7 (IL-7), in supplement to antiretroviral therapy, leads to a substantial increase of all CD4+ T cell subsets in HIV-1 infected patients. However, the quantitative contribution of the several potential mechanisms of action of IL-7 is unknown. We have performed a mathematical analysis of repeated measurements of total and naive CD4+ T cells and their Ki67 expression from HIV-1 infected patients involved in three phase I/II studies (N = 53 patients). We show that, besides a transient increase of peripheral proliferation, IL-7 exerts additional effects that play a significant role in CD4+ T cell dynamics up to 52 weeks. A decrease of the loss rate of the total CD4+ T cell is the most probable explanation. If this effect could be maintained during repeated administration of IL-7, our simulation study shows that such a strategy may allow maintaining CD4+ T cell counts above 500 cells/µL with 4 cycles or fewer over a period of two years. This in-depth analysis of clinical data revealed the potential for IL-7 to achieve sustained CD4+ T cell restoration with limited IL-7 exposure in HIV-1 infected patients with immune failure despite antiretroviral therapy.
INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; Univ. Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; INRIA, SISTM team, Bordeaux, France.
Rodolphe
R
Thiébaut
Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands.
Julia
J
Drylewicz
INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; Univ. Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; INRIA, SISTM team, Bordeaux, France.
Mélanie
M
Prague
INSERM, Unité U955, Créteil, France; Université Paris-Est, Faculté de Médecine, UMR-S955 Creteil, France.
Christine
C
Lacabaratz
CYTHERIS, Issy Les Moulineaux, France.
Stéphanie
S
Beq
INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; Univ. Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; INRIA, SISTM team, Bordeaux, France.
Ana
A
Jarne
CYTHERIS, Issy Les Moulineaux, France.
Thérèse
T
Croughs
Vaccine and Gene Therapy Institute-Florida, Port St. Lucie, Florida, United States of America.
Rafick-Pierre
RP
Sekaly
Case Western Reserve University/University Hospitals/Case Medical Center, Cleveland, Ohio, United States of America.
Michael M
MM
Lederman
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Irini
I
Sereti
INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; Univ. Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; INRIA, SISTM team, Bordeaux, France.
Daniel
D
Commenges
INSERM, Unité U955, Créteil, France; Université Paris-Est, Faculté de Médecine, UMR-S955 Creteil, France; AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Creteil, France.
Yves
Y
Lévy
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003198:Computer Simulation; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology*; D019394:Ki-67 Antigen / Q000276:immunology; D018448:Models, Immunological
C508605:IL7 protein, human; D015851:Interleukin-7; D019394:Ki-67 Antigen