Intermittent IL-2 Therapy Boosts CD4 Counts in HIV Patients

December 1, 1996

BETHESDA, Md--Intermittent infusions of interleukin-2 (aldesleukin, Proleukin) in HIV-infected patients produced "substantial and sustained" increases in the number and percentage of CD4 cells, with no associated increase in plasma HIV RNA levels, says Joseph A. Kovacs, MD, and his associates at the National Institutes of Health (NIH).

BETHESDA, Md--Intermittent infusions of interleukin-2 (aldesleukin,Proleukin) in HIV-infected patients produced "substantialand sustained" increases in the number and percentage ofCD4 cells, with no associated increase in plasma HIV RNA levels,says Joseph A. Kovacs, MD, and his associates at the NationalInstitutes of Health (NIH).

The study involved 60 HIV-infected patients with baseline CD4counts above 200/mm³ who were randomly assigned to receiveeither IL-2 plus anti-retroviral therapy or antiretroviral therapyalone.

Among the patients receiving IL-2 (every 2 months for six cyclesof 5 days each, at a starting dosage of 18 million IU/day), meanCD4 counts increased from a baseline of 428 to 916/mm³ atmonth 12, whereas counts declined in the control group from 406to 349/mm³ (N Engl J Med 335:1350-1356, 1996).

Says Dr. Kovacs, "57% of the patients treated with IL-2 hadan increase of more than 50% over the baseline CD4 count at theend of approximately 1 year."

Furthermore, these increases have been sustained for more than2 years in patients continuing to receive IL-2. In five patients,CD4 counts remained above 1,000 for at least 18 months after IL-2was stopped. "To date," Dr. Kovacs says, "no combinationof antiretroviral agents has been shown to be capable of inducingincreases in CD4 counts of this magnitude or duration."

Sustained suppression of viral replication through the use ofprotease inhibitors in combination with other agents "maylead to improved CD4 responses to IL-2 therapy," he says,citing preliminary evidence from a study of IL-2 plus indinavir(Crixivan).

A "crucial" observation, Dr. Kovacs says, is that useof IL-2 did not cause long-term increases in plasma viral load.The two groups did not differ significantly, he says, in plasmaHIV RNA or p24 antigen levels during treatment.