The addition of interleukin-2 (IL-2) to antiretroviral therapy (ART) does not confer any significant benefit in mortality or decrease in opportunistic infections in HIV-positive adults, and might increase grade 3 or 4 adverse effects, according to results of a Cochrane Database review.
A team of South African researchers reviewed a series of databases, current trials, and conference abstracts to identify randomized controlled trials (RCTs) evaluating the effects of IL-2 as an adjunct to ART in reducing morbidity and mortality in HIV-positive adults. They identified 25 eligible trials.
The researchers found no difference in mortality between the IL-2 group and the ART alone group (RR 0.97, 95% CI 0.80 to 1.17; 6 trials, 6565 participants, high certainty evidence).
Although 17 of 21 trials (n=2,600 participants) reported an increase in the CD4 cell count with the use of IL-2 compared to controls, there was little or no difference in the proportion of participants with a viral load of <50 cells/mL or <500 cells/mL by the end of the trials (RR 0.97, 95% CI 0.81 to 1.15; 5 trials, 805 participants, high certainty evidence) and (RR 0.96, 95% CI 0.82 to 1.12; 4 trials, 5929 participants, high certainty evidence) respectively.
Moreover, there was little or no difference in the occurrence of opportunistic infections (RR 0.79, 95% CI 0.55 to 1.13; 7 trials, 6,141 participants, low certainty evidence). However, there probably was an increase in grade 3 or 4 adverse events (RR 1.47, 95% CI 1.10 to 1.96; 6 trials, 6291 participants, moderate certainty evidence).
“Although antiretroviral drugs have helped to improve the quality of life and life expectancy of HIV-positive individuals, there is still a need to explore other interventions that will help to further reduce the disease burden,” the researchers note. IL-2 has emerged as a potential option because it is a cytokine that “regulates the proliferation and differentiation of lymphocytes and may help to boost the immune system.”
However, the authors concluded, “our findings do not support the use of IL-2 as an adjunct to ART in HIV-positive adults” and “further trials are not justified.”
1. Onwumeh J, Okwundu CI, Kredo T. Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults. Cochrane Database Syst Rev. 2017 May 25;5:CD009818.