The virologic, immunologic, and clinical effects of interleukin 2 with potent antiretroviral therapy in patients with moderately advanced human immunodeficiency virus infection: a randomized controlled clinical trial--AIDS Clinical Trials Group 328.
BACKGROUND
Interleukin 2 (IL-2) administration increases CD4 counts in persons with higher counts. This study investigated persons with moderately advanced human immunodeficiency virus infection receiving highly active antiretroviral therapy (HAART).


METHODS
Two hundred four patients with CD4 T-cell counts from 50/microL to 350/microL who were treatment naive or had been treated only with reverse transcriptase inhibitors began a specified protease inhibitor HAART regimen. Virologic responders (< or =5000 copies/mL) at 12 weeks were randomized to open-label continuous-infusion IL-2 (IV IL-2), subcutaneous IL-2 (SC IL-2), or HAART alone. Thirty were not randomized and 15 enrolled in a substudy, leaving 159 for analysis. Subjects continued HAART alone for 72 weeks (n = 52) or with IV IL-2 (n = 53) or SC IL-2 (n = 54) for 5 days every 8 weeks. The IV IL-2 subjects could switch to SC IL-2 if their CD4 T-cell count increased by 100/microL or by 25%.


RESULTS
Patients receiving IV or SC IL-2 had greater increases in CD4 cell counts. At week 84, median increases were 459/microL, 312/microL, and 102/microL. Increases of greater than 50% at week 60 (primary end point) were achieved in 39 patients (81%) and 32 (67%) in the IV and SC IL-2 arms, respectively, compared with 13 (29%) in the HAART arm (P<.001 for both). Treatment with IL-2 did not increase plasma human immunodeficiency virus RNA levels. There were fewer new AIDS-defining events in the IV (P = .006) and SC (P = .03) IL-2 groups than in the HAART group (0, 1, and 7, respectively). Drug-related adverse events were more frequent with IL-2 treatment.


CONCLUSIONS
Addition of IL-2 to HAART can significantly expand CD4 T-cell counts in moderately advanced human immunodeficiency virus infection, without loss of virologic control.
Mitsuyasu
Ronald
R
Department of Internal Medicine, University of California-Los Angeles, USA.
Gelman
Rebecca
R
Cherng
Deborah Weng
DW
Landay
Alan
A
Fahey
John
J
Reichman
Richard
R
Erice
Alejo
A
Bucy
R Pat
RP
Kilby
J Michael
JM
Lederman
Michael M
MM
Hamilton
Carol D
CD
Lertora
Juan
J
White
Becky L
BL
Tebas
Pablo
P
Duliege
Anne-Marie
AM
Pollard
Richard B
RB
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors
D019380:Anti-HIV Agents; D007376:Interleukin-2; D012367:RNA, Viral