NIAID clinical studies of the immune system protein interleukin-2 (IL-2) as a treatment for persons infected with HIV continue to provide encouraging results. Originally called T cell-growth factor, IL-2 is produced in the body by T cells and has potent effects on the proliferation and differentiation of a number of immune cells, including T cells, B cells and natural killer cells. Commercially, IL-2 is produced by recombinant-DNA technology.
At the XIth International Conference on AIDS, held in Vancouver, B.C., in July, NIAID scientists presented preliminary findings of a phase II study under way at the NIH Clinical Center, indicating that self-administered injections of the protein have dramatically increased levels of CD4+ T cells in patients with early HIV infection. Average increases in CD4+ T cells ranged from 28 percent to 130 percent among patients in four different dosage groups. The findings build on previous NIH reports that intravenous infusions of IL-2 can significantly boost numbers of CD4+ T cells in certain patients (see AIDS Agenda, Spring 1995).
Our data suggest that therapy with subcutaneous IL-2, in combination with antiretroviral drugs, has the potential to halt the usual progression of HIV disease by maintaining a person's CD4+ T cell count in the normal range for prolonged periods of time," says Richard T. Davey, M.D., senior investigator in NIAIDs Laboratory of Immunoregulation.
IL-2 and Quality of Life
Side effects associated with IL-2 therapy include mild to moderate flu-like symptoms such as fatigue, aches and pains and headaches. The early results of the subcutaneous IL-2 trial therefore are especially encouraging in light of other findings by NIAID investigators that HIV-infected patients receiving antiretroviral drugs plus intravenous infusions of IL-2 feel as well overall as individuals receiving antiretroviral therapy alone. Bill Barrick, RN, MSN, head nurse of the NIAID/Clinical Center HIV Research Clinic presented the findings at the XIth International Conference on AIDS in Vancouver.
In our 14-month study, we found no overall differences in quality of life or symptom distress among 15 patients receiving IL-2 and 14 not receiving IL-2," says Mr. Barrick. "Many of us had been concerned that the added symptom burden associated with intravenous IL-2 administration would be too great for HIV-infected patients to tolerate over time. The results of our study suggest otherwise, and are reassuring about the ability of people to tolerate extended therapy with intravenous IL-2."
IL-2 / protease inhibitor combo shows promise
At the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in September, NIAID scientists led by Judith Falloon, M.D., reported promising preliminary results from an ongoing study of HIV-infected volunteers treated with a combination of intravenous IL-2 and antiretroviral regimens that include the protease inhibitor indinavir. The average CD4+ T cell counts for all patients receiving the combination treatment have shown sustained increases over a one-year period.
These data suggest that IL-2, when given with a protease inhibitor such as indinavir, may have a role in treating patients with lower CD4+ T cell counts as well as those with earlier-stage disease," says Dr. Falloon. She says the combination therapy has been generally well-tolerated, with the main toxicities being the flu-like symptoms typically seen with IL-2 therapy. Toxicities typical of indinavir, such as elevated bilirubin levels and kidney stones, were also seen in some patients.
Based on these and other recent findings, NIAID investigators led by NIAID Clinical Director H. Clifford Lane, M.D., in collaboration with scientists around the world, are planning a phase III study to determine the clinical benefit of IL-2 in combination with antiretrovirals for the treatment of HIV-infected people.