Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV.
BACKGROUND
Interleukin (IL)-2 therapy impacts T-cell homeostasis. Whether IL-2 expanded CD4(+) T cells may persist following viral rebound has not been fully investigated.


METHODS
Patients with CD4(+) T cells 500/μl or more and HIV RNA less than 50 copies/ml were randomized to continue antiretroviral therapy (ART) either alone (n = 67) or combined with three IL-2 cycles (n = 81; 6 million units) twice daily for 5 days at weeks 0, 8, and 16 before stopping ART (week 24). Patients were followed up to 168 weeks.


RESULTS
At week 24, median CD4(+) T-cell counts were 1198 and 703 cells/μl in the IL-2 and control groups, respectively (P < 0.001). At week 72, 27% (IL-2 group) and 45% (control group; P = 0.03) of patients were in failure (defined as no interruption of ART at week 24, CD4 drop below 350 cells/μl or ART resumption). After week 24, a biphasic decline (before and after week 32) of CD4 was noted -106 and -7 cells/μl per month in controls and -234 and -17 in IL-2 group (all P ≤ 0.0001). At week 96, IL-2-expanded CD4(+)CD25(+) T cells remained higher than in the control group (26 vs. 16%, P = 0.006).


CONCLUSIONS
In IL-2-treated patients, CD4(+)CD25(+) T cells persisting despite viral replication allow a longer period of ART interruption.
INSERM, Unite U, Groupe Henri-Mondor Albert-Chenevier, service d'immunologie clinique, Creteil, France. yves.levy@hmn.aphp.fr
Yves
Y
Lévy
Rodolphe
R
Thiébaut
Marie-Lise
ML
Gougeon
Jean-Michel
JM
Molina
Laurence
L
Weiss
Pierre-Marie
PM
Girard
Alain
A
Venet
Philippe
P
Morlat
Béatrice
B
Poirier
Anne-Sophie
AS
Lascaux
Céline
C
Boucherie
Daniel
D
Sereni
Christine
C
Rouzioux
Jean-Paul
JP
Viard
Cliff
C
Lane
Jean-François
JF
Delfraissy
Irini
I
Sereti
Geneviève
G
Chêne
D051997:ADP-ribosyl Cyclase 1 / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016827:CD8 Antigens / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D053645:Interleukin-2 Receptor alpha Subunit / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D016827:CD8 Antigens; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D012367:RNA, Viral; D051997:ADP-ribosyl Cyclase 1