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).
The study involved 60 HIV-infected patients with baseline CD4 counts above 200/mm³ who were randomly assigned to receive either IL-2 plus anti-retroviral therapy or antiretroviral therapy alone.
Among the patients receiving IL-2 (every 2 months for six cycles of 5 days each, at a starting dosage of 18 million IU/day), mean CD4 counts increased from a baseline of 428 to 916/mm³ at month 12, whereas counts declined in the control group from 406 to 349/mm³ (N Engl J Med 335:1350-1356, 1996).
Says Dr. Kovacs, "57% of the patients treated with IL-2 had an increase of more than 50% over the baseline CD4 count at the end of approximately 1 year."
Furthermore, these increases have been sustained for more than 2 years in patients continuing to receive IL-2. In five patients, CD4 counts remained above 1,000 for at least 18 months after IL-2 was stopped. "To date," Dr. Kovacs says, "no combination of antiretroviral agents has been shown to be capable of inducing increases in CD4 counts of this magnitude or duration."
Sustained suppression of viral replication through the use of protease inhibitors in combination with other agents "may lead to improved CD4 responses to IL-2 therapy," he says, citing preliminary evidence from a study of IL-2 plus indinavir(Drug information on indinavir) (Crixivan).
A "crucial" observation, Dr. Kovacs says, is that use of IL-2 did not cause long-term increases in plasma viral load. The two groups did not differ significantly, he says, in plasma HIV RNA or p24 antigen levels during treatment.