, Volume 70, Issue 9, pp 1115–1130 | Cite as

Role of Interleukin-2 in Patients with HIV Infection

  • Sarah L. PettEmail author
  • Anthony D. Kelleher
  • Sean Emery
Review Article


Control of viral replication to below the level of quantification using combination antiretroviral therapy (ART) [cART] has led to a dramatic fall in mortality and morbidity from AIDS. However, despite the success of cART, it has become apparent that many patients do not achieve normalized CD4+ T-cell counts despite virological suppression to below the level of quantification (<50 copies/mL). Increasing data from cohort studies and limited data from clinical trials, such as the SMART study, have shown that higher CD4+ T-cell counts are associated with reductions in morbidity and mortality from both AIDS and serious non-AIDS (SNA) conditions, including cardiovascular disease. Enhancement of immune restoration over and above that achievable with ART alone, using a number of strategies including cytokine therapy, has been of interest for many years. The most studied cytokine in this setting is recombinant interleukin (IL)-2 (rIL-2).

The purpose of this review is to describe the current status of rIL-2 as a therapeutic agent in the treatment of HIV-1 infection. The review focuses on the rationale underpinning the exploration of rIL-2 in HIV infection, summarizing the phase II and III findings of rIL-2 as an adjunctive therapy to ART and the phase II studies of rIL-2 as an antiretroviral-sparing agent.

The phase II studies demonstrated the potential utility of continuous intravenous IL-2 and subsequently intermittent dosing with subcutaneous rIL-2 as a cytokine that could expand the CD4+ T-cell pool in HIV-1-infected patients without any significant detrimental effect on HIV viral load and with an acceptable adverse-effect profile. These data were utilized in designing the phase II studies of rIL-2 as an ART-sparing agent and, more importantly, the large phase III clinical endpoint studies of rIL-2 in HIV-1-infected adults, ESPRIT and SILCAAT. In the latter, subcutaneous rIL-2 was given intermittently (5 days of twice-daily dosing at 4.5–7.5 million international units per dose every 8 weeks) to HIV-1-infected adults receiving cART using an induction/maintenance strategy. Both studies explored the clinical benefit of intermittent subcutaneous rIL-2 with cART versus cART in HIV-infected adults with CD4+ T-cell counts ≥300 cells/mL (ESPRIT study) and 50–299 cells/mL (SILCAAT study). Both studies showed that receipt of rIL-2 conferred no clinical benefit despite a significantly higher CD4+ T-cell count in the rIL-2 arms of both studies. Moreover, there was an excess of grade 4 clinical events in ESPRIT rIL-2 recipients.

The results of the phase III clinical endpoint studies showed that rIL-2 has no place as a therapeutic agent in the treatment of HIV infection.


Therapeutic Vaccination Viral Rebound Opportunistic Disease Dose Cycle Clinical Endpoint Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Professor David A. Cooper for his continued advice, support and mentorship.

This study was funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. The National Centre in HIV Epidemiology and Clinical Research is affiliated with the Faculty of Medicine, University of New South Wales. None of the authors have any conflict of interest or financial interest in recombinant interleukin-2 preparations.


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© Adis Data Information BV 2010

Authors and Affiliations

  • Sarah L. Pett
    • 1
    • 2
    Email author
  • Anthony D. Kelleher
    • 1
    • 2
  • Sean Emery
    • 1
  1. 1.National Centre in HIV Epidemiology and Clinical Research, Faculty of MedicineUniversity of New South WalesCoogeeAustralia
  2. 2.Centre for Applied Medical Research (AMR)St Vincent’s HospitalSydneyAustralia

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