Press Release- not to be released before May 19, 1998

Universität GH Essen

Results of interleukin-2 (IL-2) for the immunomodulatory treatment of HIV

patients

Long-term trial of immunomodulation with interleukin-2 (IL-2) offers

alternative way for effective HIV-therapy

Until today, the standard therapy for HIV-patients consists of a

combination of highly effective antiretroviral drugs and the prophylactic

treatment against opportunistic infections. In a study, performed from 1996

through 1997 conducted by Dr. Ulrich R. Hengge, Assistant Professor at the

Department of Dermatology and Venerology, University of Essen, Germany, the

significance of additional immunmodulatory treatment with IL-2 was

examined. Interleukin-2, an important messenger for the function and

proliferation of lymphatic cells, is diminished early in the course of the

HIV disease.

In a randomised, controlled study the immunologic and virologic effects of

subcutaneous therapy with IL-2 have been examined in forty-four patients

(CD4 helper cell counts between 200 and 500 per cubicmilimeter) receiving

stable antiretroviral triple therapy (AZT, 3TC, Saquinavir). These

forty-four patients were compared to a control group of twenty patients who

received the same antiretroviral therapy, but no IL-2. The subcutaneous

injections of interleukin-2 were performed by the patients in the same way

as diabetics inject their insulin.

Besides safety and compatibility, the chairman Professor Goos and Dr.

Hengge wanted to determine the optimal time interval between single doses

of IL-2. The forty-four patients had been randomly assigned to either of

two groups: group A and group B. Group A received IL-2 every six weeks,

whereas in group B the IL-2 injections depended on the individual effect on

CD4 cell counts, the key immune cells. In group B, IL-2 was administered

when the CD4 cells declined - after an initial increase - to below the

1,25-fold of baseline CD4 cell counts.

Twenty-one patients of group A and nineteen patients of group B as well as

eighteen controls completed the 1-year study in August 1997. In both IL-2

groups the IL-2 was tolerated well. Side effects consisted in fever and

flu-like symptoms. Half of the patients showed indurations at the site of

injection. More severe side-effects (increased liver function tests and

possible reactivation of depression) were rare.

During the one-year therapy with IL-2, both groups showed an average

increase of more than 100 CD4 cells per cubicmilimeter. In group A CD4

cells increased from 370 to 492 in group A as compared from 350 to 468 in

group B, respectively. Sixteen of forty patients (40%) even showed an

increase of CD4 cell counts of more than 40% and 5 patients more than 20%,

while there was no significant change in CD4 cell counts in the control

group. In only three IL-2 treated patients CD4 cell counts decreased during

the 1-year study. In addition, both groups showed a significant increase in

natural killer cells, which exert an important role in immune defence.

To examine functional improvements, all opportunistic complications and

skin infections were registered. Until today (21 months after the start of

the study) none of the IL-2 recipients experienced an AIDS-defining event,

whereas three patients of the control group developed Kaposi's sarcomas

(tumour of skin vessels). The frequency of skin conditions, that indicate

an increasing immunodeficiency (e.g. genital warts, thrush, zoster or

herpes infections) was three to six times higher in the control group than

in both groups treated with IL-2.

The application of IL-2 was also safe in patients with concomitant

hepatitis B or C infection. Special attention was placed on alterations of

HIV viral load in blood and lymph nodes because theoretically an increase

of HIV load could occur through the stimulation of virus-infected lymphatic

cells. However, the investigators detected a slightly reduced viral load in

analysed lymph nodes, where HIV production is highest. Also, there was no

increase of HIV load in plasma. In contrast, some individuals experienced a

significant reduction of HIV load over the course of the study.

These results indicate that IL-2 is a safe and allows an effective

additional immunomodulatory treatment of HIV infection. An individual dose

adaptation (i.e. individual intervals between cycles of IL-2) sowed the

same beneficial effects with the advantage of dose and cost reduction.

Based on these promising results a European study of interleukin-2 in more

advanced individuals is in preparation, since a clinical advantage with

additional IL-2 can only be evaluated in larger studies.

Further information can be obtained (tel. 49-201-723-3649 or -2847 or by

e-mail: ulrich.hengge@uni-essen.de).

Universität GH Essen