Interleukin-2 study shows impressive results

After a year of treatment with recombinant interleukin-2, HIV-positive patients have experienced a doubling in their CD4 counts, underscoring the potential for immune-based therapies to complement antiretroviral treatment.

The study showed that the 31 patients treated with interleukin-2 had mean CD4 counts double from 428 cells at baseline to 916 cells after 12 months of interleukin-2 treatment. An additional 29 patients in the control arm of the study received only antiretroviral therapy (none were on protease inhibitors) and had a decrease in CD4 counts from 406 cells to 349 cells during the same period. No significant differences were found in HIV RNA plasma or p24 antigen levels between the two groups, nor was there an increase in viral load in the IL-2 treated patients.

The increase in CD4 cells is the highest reported in any HIV treatment, including combination therapy with protease inhibitors.

"Our study has clearly demonstrated that IL-2 therapy can have a substantial positive impact on the major immunologic abnormality associated with HIV infection — the loss of CD4 cells — without leading to an overall increase in the level of HIV in the bloodstream or to unmanageable toxicities," says Joseph Kovacs, MD, senior investigator in the critical care medicine department of the National Institutes of Health (NIH) Clinical Center in Bethesda, MD.

IL-2, originally referred to as T-cell growth factor, is manufactured by Chiron Corp. in Emeryville, CA, through recombinant DNA technology and is injected in patients during five-day treatment cycles. It is produced naturally in the body by T-cells and is effective in proliferating T-cells, B-cells, and natural killer cells.

The IL-2 therapy could complement combination therapy by helping patients strengthen their immune systems to fight opportunistic infections, say researchers.

"Complementing antiretroviral therapy with IL-2 is an attractive approach to the treatment of HIV-infected people, offering the opportunity to reduce the amount of virus in the body while boosting the immune system’s capacity," says David Cooper, MD, director of the National Center in HIV Epidemiology in Sydney, Australia, where he is working on a larger study of the therapy.

Earlier studies of higher doses of IL-2 had shown it can cause bursts of virus production in some patients. However, the current study showed that the bursts do not lead to sustained increases in viral load, Kovacs says. Moreover, because IL-2 targets the immune system rather than HIV itself, viral mutations should not reduce its effectiveness, Kovacs says.

The most common side effects during IL-2 administration were fatigue or malaise, experienced by 44% of the patients. About 8% of patients showed elevation of bilirubin levels, indicating an effect on the liver. The levels returned to normal after treatment and were not accompanied by clinical symptoms.

The study, published recently in the Oct. 31, 1996, New England Journal of Medicine, suggests that the CD4 cells induced by the IL-2 therapy were functional cells, and therefore may provide benefits by reducing opportunistic infections.

The Phase II study enrolled patients with relatively high CD4 counts. A second Phase II study is being planned for patients with more advanced HIV disease.

The NIH also is working with researchers in the United States and elsewhere to develop a Phase III study to evaluate how increased CD4 counts from IL-2 therapy will affect HIV progression and survival.