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

Arch Intern Med. 2007 Mar 26;167(6):597-605. doi: 10.1001/archinte.167.6.597.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Drug Administration Schedule
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV Infections / virology
  • Humans
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Interleukin-2 / therapeutic use*
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Time Factors

Substances

  • Anti-HIV Agents
  • Interleukin-2
  • RNA, Viral