Patients taking recombinant interleukin-2 (IL-2; Proleukin) have a larger increase in CD4 cell count following more cycles of treatment and if they have an undetectable viral load at baseline, according to an update of the ESPRIT trial presented last week at the Eleventh Annual Conference of the British HIV Association with the British Association for Sexual Health and HIV in Dublin.
IL-2 is a natural substance involved in the working of the immune system, which stimulates the production and maturation of CD4 T-cells. It is produced by T-cells to activate and recruit parts of the immune system to do their job.
Levels of IL-2 tend to fall over time in HIV infection, and low levels are associated with an increased risk of disease progression. Investigators are interested in whether it is beneficial to treat people with HIV with an artificial 'recombinant' form of IL-2 to boost immune functioning and delay disease progression.
ESPRIT (evaluation of subcutaneous Proleukin in a randomized trial) is an international, phase III study examining the effects of recombinant IL-2 (rIL-2) injections on the progression of HIV disease and death.
The trial enrolled HIV-positive patients with a CD4 cell count of at least 300 cells/mm3 who were taking antiretroviral therapy. The patients were randomised to receive injections of rIL-2 under the skin alongside their antiretroviral therapy, or to receive antiretroviral therapy alone.
The patients received three cycles of rIL-2 injections, followed by additional cycles as required to maintain CD4 cell counts above twice the baseline level or 1000 cells/mm3.
ESPRIT is an ‘open label’ trial, meaning that the patients and healthcare workers are aware of whether or not they are taking rIL-2.
Of the 1977 patients receiving rIL-2, 909 (46%) had experienced a CD4 cell count rise of at least 200 cells/mm3 after a median of 36 months’ follow-up. Using a multivariate logistic regression analysis, the investigators found that these patients were twice as likely to have a viral load of 50 copies/ml or less when they began rIL-2 injections than those with a smaller CD4 cell count rise (adjusted odds ratio [OR]: 2.03; p
They also found that more of these patients had completed four or more cycles of rIL-2 treatment (adjusted OR: 2.52; p
Patients with a higher minimum (‘nadir’) CD4 cell count also had a better outcome in response to rIL-2 (adjusted OR: 1.08; p 3 by 8% (adjusted OR: 0.92; p = 0.001).
There were no significant effects of age, CD4 cell count at the start of the study, or stage of HIV disease on treatment outcome.
IL-2 use in HIV therapy is unlicensed and experimental. In the United Kingdom, it is currently only available for patients within clinical trials such as ESPRIT, or in exceptional circumstances. Although it may increase CD4 cell counts in patients with poor responses to anti-HIV treatment, its use is associated with rises in viral load and substantial side-effects.
Nuwagaba-Biribonwoha H et al. Predictors of current CD4+ T-cell response among patients receiving subcutaneous recombinant interleukin-2 (RIL-2) in ESPRIT (evaluation). Eleventh Annual Conference of the British HIV Association with the British Association for Sexual Health and HIV, Dublin, abstract O24a, 2005.