Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults

Onwumeh, Jennifer ; Okwundu, Charles I. ; Kredo, Tamara (2017)

CITATION: Onwumeh, J., Okwundu, C. I. & Kredo, T. 2017. Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults. Cochrane Database of Systematic Reviews, 5:1-68, Art. CD009818, doi:10.1002/14651858.CD009818.pub2.

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Background: Human immunodeficiency virus (HIV) continues to be a leading cause of morbidity and mortality, particularly in sub‐Saharan Africa. 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. One potential strategy is the use of interleukin‐2 (IL‐2) in combination with antiretroviral therapy (ART). IL‐2 is a cytokine that regulates the proliferation and differentiation of lymphocytes and may help to boost the immune system. Objectives: To assess the effects of interleukin‐2 (IL‐2) as an adjunct to antiretroviral therapy for HIV‐positive adults. Search methods: We searched the following sources up to 26 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; the Web of Science; LILACS; the World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP); and We also checked conference abstracts, contacted experts and relevant organizations in the field, and checked the reference list of all studies identified by the above methods for any other potentially eligible studies. Selection criteria: Randomized controlled trials (RCTs) that evaluated the effects of IL‐2 as an adjunct to ART in reducing the morbidity and mortality in HIV‐positive adults. Data collection and analysis:Two review authors independently screened records and selected trials that met the inclusion criteria, extracted data, and assessed the risk of bias in the included trials. Where possible, we compared the effects of interventions using risk ratios (RR), and presented them with 95% confidence intervals (CI). We assessed the overall certainty of the evidence using the GRADE approach. Main results: Following a comprehensive literature search up to 26 May 2016, we identified 25 eligible trials. The interventions involved the use of IL‐2 in combination with ART compared with ART alone. There was no difference in mortality apparent 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). Seventeen of 21 trials reported an increase in the CD4 cell count with the use of IL‐2 compared to control using different measures (21 trials, 7600 participants). Overall, there was little or no difference in the proportion of participants with a viral load of less than 50 cells/mL or less than 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. Overall there may be little or no difference in the occurrence of opportunistic infections (RR 0.79, 95% CI 0.55 to 1.13; 7 trials, 6141 participants, low certainty evidence). There was probably 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). None of the included trials reported adherence. Authors' conclusions: There is high certainty evidence that IL‐2 in combination with ART increases the CD4 cell count in HIV‐positive adults. However, IL‐2 does not confer any significant benefit in mortality, there is probably no difference in the incidence of opportunistic infections, and there is probably an increase in grade 3 or 4 adverse effects. Our findings do not support the use of IL‐2 as an adjunct to ART in HIV‐positive adults. Based on our findings, further trials are not justified.

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