In an early report from an ongoing, randomized clinical trial, researchers from
the University of California, San Francisco have shown that the addition of the
immune stimulator interleukin-2 (IL-2) to highly active antiretroviral therapy
(HAART) improves immune function in patients who have been recently infected
Results in 20 patients were reported today (July 12) by Frederick M. Hecht, MD,
assistant clinical professor with the UCSF Positive Health Program at San
Francisco General Hospital Medical Center. He presented the findings at the
XIII International AIDS Conference in Durban, South Africa.
“Adding IL-2 to HAART in this early period significantly improved CD4 cell
counts” said Hecht.
Researchers are particularly interested in studying persons who start HAART
within months of becoming HIV infected because these individuals may have
better preserved immune responses to HIV—responses that may be destroyed by
the virus in the first year of infection. Researchers are trying to determine
whether adding IL-2 to HAART in persons who begin treatment in this early phase
of infection increases CD4 counts and bolsters immune responses to HIV.
Participants were recruited by the UCSF Options Project, based at SFGHMC, which
is conducting clinical, behavioral, epidemiological, and pathogenesis studies
of the earliest stage of HIV infection, called primary infection.
Study participants must begin antiretroviral therapy within 12 months of
becoming infected, and most start therapy within 6 months of infection, said
All patients received HAART with a combination of three drugs. Half of the
patients were randomly assigned to supplement their medication with IL-2 early
in the study. These patients began receiving IL-2 four weeks after HAART had
suppressed the amount of virus in their blood to a specific point (less than
500 RNA copies/ml). The remaining patients were slated to begin IL-2 therapy
later, 48 weeks after the amount of virus in their blood dropped below the
IL-2 is a powerful immune modulator, but it must be used with care in HIV
patients because it has the potential to stimulate replication of HIV in
infected cells, said Hecht. For this reason, the study was designed to ensure
that patients did not take IL-2 until antiretroviral therapy was effectively
blocking HIV replication.
Since the use of IL-2 was delayed in one group of patients, they were able to
serve as a control group for those receiving IL-2 early in the study.
Researchers were able to compare CD4 cell counts and other measures of immune
function in the early IL-2 patients with those who initially received
antiretroviral therapy alone.
“We divided the patients into early and late treatment groups in an effort to
find out if use of IL-2 is helpful to patients with early HIV infection, and to
see if results differ depending on how soon after infection IL-2 treatment is
started,” said Hecht.
Interleukin-2 was administered subcutaneously in what is considered a standard
high-dose cycle (twice daily for five days every eight weeks for a total of
six treatment cycles).
At the Durban meeting, Hecht reported on results in 20
patients, 9 in the early IL-2 group and 11 in the deferred IL-2 treatment
group. All the patients in the early IL-2 group experienced the side-effects
common to treatment with this immune stimulator, including fever and chills.
After 48 weeks of antiretroviral treatment, the average CD4 cell count was
2,002 (up from 584) in the early IL-2 group and 706 (up from 451) in the
delayed group, a statistically significant difference.
In addition, the amount of virus in the blood had fallen to very low levels
(less than 50 RNA copies/ml) in most patients in both treatment groups,
providing a reassuring indication that the addition of IL-2 to HAART should not
increase HIV replication, said Hecht.
“We will continue to follow these patients to see whether the immunological
benefit that adding IL-2 to HAART appears to confer will improve the
effectiveness of HAART over time, and whether there is other evidence of
better immunologic control of HIV,” said Hecht. The researchers will also look
at whether persons who stop HAART treatment after receiving IL-2 maintain
strong control of HIV replication.
Co-investigators included James O. Kahn, MD, UCSF Positive Health Program at
SFGHMC; Margaret Chesney, PhD, UCSF Center for AIDS Prevention Studies; Robert
Grant, MD, UCSF School of Medicine and the UCSF-affiliated Gladstone Institute
of Immunology and Virology; Michael P. Busch, MD, PhD, UCSF Department of
Laboratory Medicine and the Blood Centers of the Pacific; Jorge Oksenberg,
MD, UCSF Department of Neurology; Michael McGrath, MD, PhD, UCSF School of
Medicine and SFGHMC; Jay A. Levy, MD, UCSF School of Medicine and UCSF AIDS
Research Institute; and Marcus Altfeld, MD, and Bruce Walker, MD,
Massachusetts General Hospital and Harvard Medical School;