By Charles Craig

A National Institutes of Health (NIH)-sponsored clinical study using interleukin-2 (IL-2), also called T cell growth factor, to boost proliferation of CD4 cells to fight AIDS, in combination with antiviral drugs, showed patients experienced marked increases in immune system cells without an overall jump in amount of HIV.

The next step, said Richard Davey, senior investigator of the NIH's National Institute of Allergy and Infectious Diseases (NIAID), is to conduct a Phase III trial to assess the clinical benefit of attacking HIV by accelerating proliferation of the CD4 T cells the virus infects. HIV's immune system cell destruction is what eventually kills AIDS patients.

Although AIDS research has established that HIV employs activated CD4 cells to replicate and spread to other CD4 cells, Davey said the IL-2 trial demonstrated use of the T cell growth factor significantly boosted T cells without increasing the amount of virus.

The study also showed elevated CD4 cell counts were sustained for more than three years with continued use of IL-2, which was supplied by Chiron Corp., of Emeryville, Calif.

Davey said the trial, which involved 18 HIV patients, revealed a "transient increase" in HIV, but he added the net effect was "exceedingly high increases in CD4 cells" and no significant jump in viral load during the trial.

Results of the study by Davey and colleagues at NIAID are published in the April issue of the Journal of Infectious Diseases.

Another significant finding in Davey's trial revealed subcutaneous IL-2 injections reduced toxicities associated with intravenous infusions of IL-2. Patients, who administered the drug themselves at home, still suffered flu-like symptoms, such as fatigue, pain and headaches, but the side effects were less severe.

Davey said a Phase III trial, which is in the planning stages with international AIDS study groups, would take three to five years to complete. It would attempt to evaluate in patients with early-stage HIV the ability of IL-2 and antiviral drugs, such as combinations of nucleoside analogues and protease inhibitors, to reduce AIDS-related opportunistic infections and extend patients' lives.

Chiron markets IL-2 as Proleukin for treatment of metastatic kidney cancer. The company has patent protection for all treatment uses of IL-2. If the Phase III AIDS trial is successful, Chiron would file for FDA approval to expand the label on Proleukin to include HIV. The company will continue to supply IL-2 for the Phase III study and may provide funding. The trials also use Chiron's branch DNA test for measuring the amount of HIV in a patient's system.

Chiron officials noted the sustained increases in CD4 T cell counts with IL-2 were higher than levels achieved with antiviral drugs alone.

The nucleoside analogues and protease inhibitors approved to attack HIV replication have been cleared for marketing based on their ability to reduce the amount of virus in the blood stream and increase CD4 cell counts.

More Confirmation That IL-2 Works

Davey's findings confirmed an earlier NIAID trial showing intravenous administration of IL-2 boosted the number of CD4 T cell levels in HIV patients. (See BioWorld Today, Oct. 31, 1996, p. 1.) Primary goals of the most recent study were to determine if subcutaneous injections could produce results as effective as intravenous infusions with less toxicity.

In the trial, 18 HIV patients with CD4 cell counts greater than 200 were enrolled and were treated with IL-2 for a minimum of six months. A year after treatment began, CD4 cell counts jumped by 200 in eight patients and by 0 to 200 in six others. Four patients experienced a decline in CD4 counts.

Of eight patients who continued to receive IL-2 for three years, five sustained CD4 cell counts between 800 and 2,000 and three maintained levels in the range of 400 to 600.

The higher a patient's T cell count at the start of the trial, the better the response to IL-2.

Healthy people typically have CD4 cell counts between 600 and 1,200.

Chiron's stock (NASDAQ:CHIR) closed Monday at $19.609, down $0.016. *