HIV Patients Get Long-Term Boost with Short, Intermittent Drug Regimen
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
For information about AIDS treatment or to enroll in a clinical
study, please contact www.AIDSinfo.nih.gov
or call: 1-800-HIV-0440 (1-800-448-0440).
NIAID is a component of the National Institutes of Health (NIH),
an agency of the U.S. Department of Health and Human Services. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on transplantation
and immune-related illnesses, including autoimmune disorders, asthma
and allergies. Press releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Reference: CE Farel et al. Induction and maintenance
therapy with intermittent interleukin-2 in HIV-1 infection. Blood
103:3282-86. Published online January 15, 2004.DOI: 10.1182/blood-2003-09-3283.