Continuing or adding IL-2 in patients treated with antiretroviral therapy (ACTG Protocol A5051, a rollover trial of ACTG Protocol A328)

The patients previously receiving IL-2 continued to have elevated CD4 levels with extended use of IL-2. The prior ART-alone recipients had increases in CD4 levels to comparable levels as the prior IL-2 recipients (median 804 versus 847 cells/mm3 at week 72; 60% versus 9% had >50% increase in A5051 to week 72, p < 0.001). Those who had previously received IL-2 required fewer IL-2 cycles to maintain their CD4 T-cell counts compared to those newly initiating IL-2. The treatments were well tolerated with no significant differences in toxicity or discontinuations between those newly versus previously receiving IL-2. There were few clinical events observed.Although sustained CD4 T-cell count increases were seen with IL-2 administration as in other studies, the absence of clinical benefit in two recent randomized trials has demonstrated no apparent role for IL-2 as a therapy in HIV disease.A5051 ClinicalTrials.gov Identifier: NCT00000923.In HIV infection, CD4 cell number progressively decreases, predisposing affected individuals to the development of opportunistic infections or malignancies if they are left untreated. Effective antiretroviral therapy reduces HIV-1 RNA levels, improves CD4 counts, and lowers the risk of opportunistic infections and malignancies. Interleukin-2 (IL-2) has been shown to increase CD4 T-cell numbers mainly by expanding CD4 cells and by prolonging their half-lives [1-3].AIDS Clinical Trial Group (ACTG) study A5051 was an open-label study that explored continuation therapy with IL-2 for patients who had participated in A328 [4]. A328 enrolled patients with little or no prior antiretroviral experience and CD4 T cell counts between 50 and 350 cells/mm3 who were then treated with a 12-week course of protease inhibitor-containing antiretroviral therapy. If their HIV-1 RNA was less than 5,000 copies/ml, they were randomized to continue antiretroviral therapy (ART) alone or with either IV or subcutaneous IL-2. The study showed that IL-2 significantly ex