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.

TitleThe 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.
Publication TypeJournal Article
Year of Publication2007
AuthorsMitsuyasu R, Gelman R, Cherng DWeng, Landay A, Fahey J, Reichman R, Erice A, R Bucy P, J Kilby M, Lederman MM, Hamilton CD, Lertora J, White BL, Tebas P, Duliege A-M, Pollard RB
Corporate AuthorsAIDS Clinical Trials Group 328 Study Team
JournalArch Intern Med
Volume167
Issue6
Pagination597-605
Date Published2007 Mar 26
ISSN0003-9926
KeywordsAdolescent, Adult, Aged, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Administration Schedule, Female, HIV Infections, Humans, Infusions, Intravenous, Injections, Subcutaneous, Interleukin-2, Male, Middle Aged, RNA, Viral, Time Factors
Abstract

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.

CONCLUSION: 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.

DOI10.1001/archinte.167.6.597
Alternate JournalArch. Intern. Med.
PubMed ID17389292
Grant ListAI25859 / AI / NIAID NIH HHS / United States
AI25868 / AI / NIAID NIH HHS / United States
AI25879 / AI / NIAID NIH HHS / United States
AI25903 / AI / NIAID NIH HHS / United States
AI25924 / AI / NIAID NIH HHS / United States
AI27600 / AI / NIAID NIH HHS / United States
AI27658 / AI / NIAID NIH HHS / United States
AI27661 / AI / NIAID NIH HHS / United States
AI27673 / AI / NIAID NIH HHS / United States
AI32782 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI39156 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
RR-00032 / RR / NCRR NIH HHS / United States
RR-00044 / RR / NCRR NIH HHS / United States
RR-00046 / RR / NCRR NIH HHS / United States
RR-00080 / RR / NCRR NIH HHS / United States
RR-00865 / RR / NCRR NIH HHS / United States
RR-05096 / RR / NCRR NIH HHS / United States