Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment.
HIV infection results in CD4+ T cell deficiency, but efficient combination antiretroviral therapy (c-ART) restores T cells and decreases morbidity and mortality. However, immune restoration by c-ART remains variable, and prolonged T cell deficiency remains in a substantial proportion of patients. In a prospective open-label phase I/IIa trial, we evaluated the safety and efficacy of administration of the T cell regulator IL-7. The trial included 13 c-ART-treated HIV-infected patients whose CD4+ cell counts were between 100 and 400 cells/microl and plasma HIV RNA levels were less than 50 copies/ml. Patients received a total of 8 subcutaneous injections of 2 different doses of recombinant human IL-7 (rhIL-7; 3 or 10 microg/kg) 3 times per week over a 16-day period. rhIL-7 was well tolerated and induced a sustained increase of naive and central memory CD4+ and CD8+ T cells. In the highest dose group, 4 patients experienced transient increases in viral replication. However, functional assays showed that the expanded T cells responded to HIV antigen by producing IFN-gamma and/or IL-2. In conclusion, in lymphopenic HIV-infected patients, rhIL-7 therapy induced substantial functional and quantitative changes in T cells for 48 weeks. Therefore, patients may benefit from intermittent therapy with IL-7 in combination with c-ART.
Levy
Yves
Y
1INSERM U955, Université Paris 12, and Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Creteil, France. yves.levy@hmn.aphp.fr
Lacabaratz
Christine
C
Weiss
Laurence
L
Viard
Jean-Paul
JP
Goujard
Cecile
C
Lelièvre
Jean-Daniel
JD
Boué
François
F
Molina
Jean-Michel
JM
Rouzioux
Christine
C
Avettand-Fénoêl
Véronique
V
Croughs
Thérèse
T
Beq
Stéphanie
S
Thiébaut
Rodolphe
R
Chêne
Geneviève
G
Morre
Michel
M
Delfraissy
Jean-François
JF
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002453:Cell Cycle / Q000187:drug effects; D004361:Drug Tolerance; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000009:adverse effects / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D008231:Lymphopenia / Q000188:drug therapy / Q000276:immunology; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012449:Safety; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
C508605:IL7 protein, human; D015851:Interleukin-7; D011994:Recombinant Proteins