Effects of interleukin-2 plus highly active antiretroviral therapy on HIV-1 replication and proviral DNA (COSMIC trial).
BACKGROUND
The effect of interleukin-2 (IL-2) in combination with antiretroviral therapy on HIV-1 replication and reservoirs was investigated.


METHODS
In a prospective, open-label trial, 56 asymptomatic HIV-1-infected subjects (CD4 T cell count > 350 x 10(6) cells/l) were randomized to highly active antiretroviral therapy (HAART: stavudine, lamivudine, nelfinavir, saquinavir) with or without IL-2 (9 megaunits daily for 5 days in 6-weekly intervals for a total of eight cycles). Productive and latent infection were analysed in peripheral blood, and residual virus replication in the lymphoid tissue and in the cerebrospinal fluid. The influence of IL-2 on viral rebound after treatment discontinuation was studied.


RESULTS
Virus replication was detected in 21 of 31 on-treatment lymph nodes despite undetectable plasma viraemia. Viral RNA was found in resting as well as in proliferating cells. RNA-negative patients tended towards more rapid proviral DNA elimination. Supplementary IL-2 led to a greater increase in CD4 T cell counts than HAART alone (P < 0.001), resulting in normalization in approximately 90% of IL-2-treated patients compared with approximately 50% HAART-only subjects. IL-2 had no beneficial effect on virus replication and on proviral DNA in peripheral blood.


CONCLUSIONS
Viral persistence during HAART is partly a result of continued low-level replication, calling for more active regimens. IL-2 accelerates the normalization of CD4 T cell counts but does not impact on virus production or latency.
Stellbrink
Hans-Jürgen
HJ
Department of Medicine, Eppendorf University, Hamburg, Germany.
van Lunzen
Jan
J
Westby
Michael
M
O'Sullivan
Eithne
E
Schneider
Claus
C
Adam
Axel
A
Weitner
Lutwin
L
Kuhlmann
Birger
B
Hoffmann
Christian
C
Fenske
Stefan
S
Aries
Philipp S
PS
Degen
Olaf
O
Eggers
Christian
C
Petersen
Heiko
H
Haag
Friedrich
F
Horst
Heinz A
HA
Dalhoff
Klaus
K
Möcklinghoff
Christiane
C
Cammack
Nick
N
Tenner-Racz
Klara
K
Racz
Paul
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008198:Lymph Nodes / Q000187:drug effects / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011533:Proviruses / Q000187:drug effects* / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D014766:Viremia / Q000188:drug therapy; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D007376:Interleukin-2; D012367:RNA, Viral