In a study at the National Institutes of Health (NIH), HIV-infected patients receiving antiretroviral drugs plus bimonthly, five-day infusions of interleukin-2 (IL-2) reported feeling as well overall as individuals receiving antiretroviral therapy alone, despite the side effects during the infusions.
Previously, the NIH investigators have found that intermittent infusions of high doses of IL-2, given in conjunction with antiretrovirals, can significantly boost CD4+ T cell counts in some HIV-infected patients (see New England Journal of Medicine, March 2, 1995). Subsequently, it has become clear that lower doses of IL-2 can increase CD4+ T cell counts with less toxicity.
In conjunction with those reports, the new findings are very encouraging, says H. Clifford Lane, M.D., NIAID clinical director. "Now we know that the increases in CD4+ T cells seen with IL-2 therapy do not come at the expense of a patient's overall quality of life. This reinforces our view that IL-2 therapy will have an important role in preserving the immune systems of some HIV-infected individuals."
Bill Barrick, RN, MSN, head nurse of the National Institute of Allergy and Infectious Diseases/Clinical Center (CC) HIV Research Clinic will present his group's findings on quality of life in a poster session at the XIth International Conference on AIDS in Vancouver, British Columbia, on Wednesday, July 10.
In this 14-month study, we found no overall difference 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 HIV-infected people to tolerate extended therapy with intravenous IL-2."
In the current study, Mr. Barrick and colleagues studied are presentative subset of patients who were participating in a randomized, controlled clinical trial of intravenous infusions of IL-2. Joseph A. Kovacs, M.D., principal investigator of the trial, reported preliminary virologic and immunologic data from the overall study group at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy in September 1995 (abstract LB-8).
Mr. Barrick, Dr. Kovacs and their team administered two questionnaires, over a 14-month study period, to 29 study patients. Fifteen of these patients were receiving IL-2 infusions for five consecutive days every two months in addition to approved antiretroviral drugs; a control group of 14 patients was receiving only approved antiretroviral agents.
The first questionnaire focused on patients' perceptions of their health and overall physical, psychological, cognitive and social functioning. This questionnaire was administered monthly to both the IL-2 patients and the control patients.
The second questionnaire queried patients about their symptoms. This questionnaire was administered to IL-2 patients before each five-day infusion cycle, each day during the cycle, the day after the treatment cycle, and 30 days later. Control patients completed this questionnaire once a month.
With the first questionnaire, the investigators assessed how the patients perceived the following:
* Overall health. Patients responded to questions about physical, personal, emotional, occupational and overall feelings in terms of "the best I ever felt" to "the worst I ever felt."
* Physical functioning. Patients responded to questions about the extent to which their physical and emotional health had interfered with activities such as heavy lifting, running, walking up stairs, eating, dressing, etc.
* Psychologic and cognitive functioning. Patients responded to questions about how they felt, and how "things have been going." Questions included indicators of anxiety, depression, and changes in mental function.
* Social and role functioning. Patients responded to questions about functioning in a social milieu including social activities, work activities, and remaining in bed due to not feeling well.
Although the investigators found no overall difference between the IL-2 and control groups using these measures, two scales -- physical functioning and social and role function -- showed slight benefit in the IL-2 group that did not reach statistical significance. An analysis of changes in patients' weight also suggested a slight weight gain in the IL-2 group that did not reach statistical significance.
In their assessment of symptom burden, the researchers found that patients receiving IL-2 reported an increased severity of symptoms during their IL-2 infusions, but in the overall study period, fared as well as patients receiving antiretroviral drugs alone.
"In our studies, intravenous IL-2 infusions generally have produced mild to moderate symptoms akin to the flu by days four and five of treatment," says Dr. Kovacs. "These symptoms generally resolve within 48 hours of the end of the five-day cycle, and do not increase in severity during the later cycles of IL-2."
Mr. Barrick's and Dr. Kovacs' colleagues on the quality of life study include Susan E. Vogel, RN, BSN; Faith Dugan, RN; Jane Engle, RN, MSN; the nursing staff of the HIV Research Clinic and Dr. Lane.
IL-2, originally called T cell-growth factor, 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 and is licensed for a kind of kidney cancer. The recombinant IL-2 used in the NIAID study was produced by Chiron Corporation of Emeryville, Calif.
Current studies of IL-2 build on 14 years of NIAID research into the role of IL-2 in the immune system and its possible use as an HIV therapy. In 1982, before the identification of HIV as the cause of AIDS, Dr. Lane and collaborators from the U.S. Food and Drug Administration demonstrated that IL-2 could enhance the activity of immune system cells taken from AIDS patients. In 1983, the first AIDS patients were infused with IL-2, during the same period when cancer patients were first treated with the substance.
Over the next 12 years, NIAID and CC researchers refined their approach to IL-2 therapy for HIV infection through an ongoing series of laboratory experiments and small clinical trials.
As mentioned above, Dr. Kovacs, Dr. Lane and their colleagues reported in 1995 that intermittent infusions of IL-2 significantly boosted levels of CD4+ T cells in some patients for more than two years in an open-label study.
Preliminary results of a randomized study of intermittent, intravenous IL-2 therapy were presented last fall; final results have been submitted for publication.
NIAID and CC are components of the National Institutes of Health. NIAID conducts and supports research to prevent, diagnose and treat illnesses such as AIDS and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.
Barrick B, et al. Quality of life and symptom distress in HIV-infected persons receiving intravenous interleukin-2 (IL-2). XIth International Conference on AIDS (Abstract # 2306), Vancouver, July 7-12, 1996.
Kovacs JA, et al. Increases in CD4 lymphocytes with intermittent courses on interleukin-2 in patients with human immunodeficiency virus infection. N Engl J Med 1995;332(9):567-75.
Kovacs JA, et al. Randomized trial of intermittent interleukin-2 therapy in HIV-infected patients with CD4 counts >200 cells/mm3. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy (Abstract LB-8), San Francisco, Sept. 17-20, 1995.
NIAID press releases, fact sheets and other materials are available on the Internet via the NIAID home page. The address is http://www.niaid.nih.gov.