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Interleukin 2 increases CD4 T cell counts in people with HIV

BMJ 2000; 321 doi: (Published 22 July 2000) Cite this as: BMJ 2000;321:198
  1. Deborah Josefson
  1. San Francisco

    Adding interleukin 2 to antiretroviral drugs substantially increases the CD4 T cell count and decreases the viral load of HIV, according to a multicentre trial sponsored by the National Institutes for Health (JAMA 2000;284:183-9).

    The combination treatment may further extend the immune competency and therefore the life span of people infected with HIV. The two year study, led by Drs Richard Davey Jr and H Clifford Lane of the National Institute for Allergy and Infectious Diseases, enrolled 82 patients and randomised them into two groups. Nearly all the patients were male.

    Forty three patients received antiretroviral drugs alone, and 39 patients received antiretroviral drugs plus intermittent therapy with subcutaneous interleukin 2 at a starting dose of 7.5 mIU twice a day for five days every eight weeks.

    The choice of antiretroviral was left to the patients and their physicians, but both groups had similar proportions of patients who were taking protease inhibitors (89% of those in the interleukin group; 80% of those taking only an antiretroviral). Patients with serious AIDS defining illnesses were excluded from the study.

    Enrolment criteria included either a baseline CD4 count of 200-500x106 or 14% of all T cells, a viral load of less than 10 000 copies of HIV-1 RNA, and no previous treatment with interleukin 2.

    Additionally, patients had to be free of treatment with systemic steroids, chemotherapy, and cytotoxic agents for at least four weeks before the trial.

    Of the initial 82 patients enrolled, 78 completed the study. After one year, patients who had been receiving both interleukin 2 and antiretroviral drugs sustained a greater increase in CD4 counts than those on antiretrovirals alone, with an average increase of 112% compared with 18%. CD8 cells showed no substantial difference between the two study arms.

    Moreover, there was a dose related increase in CD4 count with increasing dose of interleukin 2, and the CD4 count continued to rise with subsequent cycles. Patients taking the highest dose of interleukin 2 had an average rise in CD4 count of 207%, compared with a 39% rise for the patients taking low dose interleukin 2.

    HIV suppression was also greater in the subset treated with interleukin 2, and 67% of those taking interleukin 2 achieved a viral load of less than 50 copies of HIV per millilitre of blood, which in some assays is at the “undetectable” level. In contrast, only 37% of those taking antiretrovirals alone achieved that level of suppression.

    The latter result is somewhat surprising because studies performed in the era before antiretrovirals suggested that administration of interleukin 2 caused a transient increase in viraemia.

    Treatment with interleukin 2 was generally well tolerated, but common adverse effects included influenza-like syndromes, with fever, sweats, and myalgias. These were controlled with ibuprofen, acetaminophen, hydration, rest, and lowering of dose if necessary.

    More serious adverse events occurred in three patients taking interleukin 2 with thrombophlebitis, mania, and bilirubinaemia. Additionally, one patient taking interleukin 2 died during the study period from hepatocellular carcinoma.

    Although the study results are promising, it is still unclear if they would translate into long term gains. Consequently, two large international studies are under way to confirm the results and see if they are clinically beneficial.

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