National Institutes of Health (NIH) scientists report that brief, widely-spaced courses of the experimental immune-boosting drug interleukin-2 (IL-2) allow people with HIV to maintain near normal levels of a key immune system cell for long periods. The researchers, from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and the Warren G. Magnuson Clinical Center, describe their findings in the May 1 issue of the journal Blood.
"These data provide strong evidence that IL-2 therapy, which can be self-administered by patients, could be an important adjunct to highly active antiretroviral therapy (HAART)," says NIAID Deputy Director John R. La Montagne, Ph.D.
The new report summarizes the experience of 77 HIV-positive individuals who enrolled in extension phases of three long-running AIDS clinical trials. Participants were taught to inject themselves subcutaneously with IL-2 twice daily in 5-day-long cycles. Cycles were initiated as often as necessary to maintain levels of immune cells called CD4+ T cells at predetermined, individually tailored amounts. HIV infection causes progressive loss of CD4+ T cells. Without enough of these "helper" immune cells, people with HIV disease have a hard time fending off infections. IL-2 can boost CD4+ T cell levels, with the goal of improving overall immune health.
Because HIV infection causes progressive immune destruction, it stands to reason that immune-stimulation therapy, such as IL-2, might play a substantial role in treating patients with this condition, notes Richard Davey, Jr., M.D., an NIAID AIDS clinician who headed the studies reported in Blood. Indeed, during the early 1980s NIH physicians pioneered the use of long courses of IL-2 to treat individuals whose immune systems had mysteriously failed. Scientists now know those people were suffering from AIDS, but at the time the virus causing AIDS had yet to be identified.
Although NIH physicians have accumulated over 20 years of experience with IL-2 therapy, the most impressive results began to appear in the early 1990s when the doctors started treating patients with short, intermittent cycles of the drug, Dr. Davey says. Today, HIV patients receiving IL-2 therapy typically begin with 5-day-long cycles every other month while taking drugs, such as HAART, on a sustained basis. According to Dr. Davey, this regimen often raises an HIV patient's CD4+ T cell levels well into the normal range after only a few cycles. The new research suggests IL-2 therapy can then be administered much less frequently without loss of benefit.
Most studies to date have looked at IL-2 therapy only over relatively short periods, says Dr. Davey. In contrast, the average length of patient follow-up described in the current paper is about six years. Patients in these trials have received an average of 10 IL-2 cycles during the course of their involvement, with most of the cycles occurring in the initial years of participation. Of the original 77 volunteers, 61 achieved and maintained normal or nearly normal levels of CD4+ T cells for periods ranging from two to 91 months between IL-2 cycles. During the most recent period of study, the average time between cycles was more than 3 years. (Of the 16 people no longer participating, one died, one developed non-Hodgkin's lymphoma, eight elected to follow other treatment plans and six experienced CD4 cell count declines that did not respond to IL-2 therapy.)
"Patients described in this study are still being followed," says Dr. Davey. "There are also trials planned or underway to learn if IL-2 therapy could delay or obviate the need for continuous HAART, thereby sparing persons with HIV disease from the serious side-effects that HAART can cause. The early experience from some small preliminary studies in this area suggests that this may indeed be a possibility, although larger trials are clearly needed to explore this fully."