Immune-based therapy is considered by many to be the "holy grail" of AIDS research. Most successful therapies to date have been anti-HIV drugs that suppress reproduction of HIV, the virus that causes AIDS. Success, however, usually comes at the price of many side effects. Researchers and patients alike have longed for therapy that doesn't so much try to wage war against the virus, but rather strengthens the weakening immune response associated with AIDS. The hope is that such an approach might be more natural or less toxic. Although health food stores offer an abundance of products that claim to "boost" or "strengthen" immunity, these are mostly just advertising claims. Helping the immune system in its battle against HIV is far more complex than simply "boosting" anything.
IL-2 or interleukin-2 is a chemical messenger of the immune system which, among other things, causes T-cells to quickly divide and reproduce, thus increasing their numbers. The body naturally produces IL-2 to help in its battles against a variety of infections by quickly growing an army of T-cells to fight the invader. IL-2 was one of the first products ever tested against AIDS because it was clear from the earliest years of AIDS research that the body was not producing its normal level of T-cells. The decline in the number of one type of T-cell, called CD4+ T-cells, is one of the easily measured characteristics of HIV disease. Most studies of IL-2 in HIV disease have used IL-2 alone or in combination with standard antiviral drugs.
One new study compared the use of IL-2 against a therapeutic vaccine known as Remune. IL-2 was administered in five-day cycles, every four weeks for the first three cycles then every six weeks for subsequent cycles. Remune was administered once every three months.
After four months, those receiving only anti-HIV therapy or anti-HIV therapy with HIV-1 Immunogen experienced an increase in CD4+ cell counts of about 100 cells. Those receiving anti-HIV therapy combined with IL-2 showed more pronounced CD4+ cell count increases, of about 750. People in all three groups showed better immune responses to HIV, though the highest percentage of people with these increased responses received Remune. Whether this corresponds to better immune control of HIV remains unknown.
The vast majority, in all three groups, had viral load decreases to below the limit of detection of the test. As time went on, the number of people with optimal viral suppression increased steadily through week 48. However, after week 48, additional increases in CD4+ cell counts among the three groups were not noted.
A very small study of low dose IL-2 given daily, was presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy and follow-up information was presented at the recent Human Retrovirus conference. The study produced puzzling results while the conference presentation created quite a buzz among the participants.
Volunteers who started anti-HIV therapy and experienced optimal viral suppression added IL-2 to their treatment regimen. They then stopped anti-HIV therapy but continued taking IL-2. After stopping anti-HIV therapy, HIV RNA levels initially rose, but then fell to levels lower than what had been observed prior to starting anti-HIV therapy.
What's important to note is that IL-2 without anti-HIV therapy didn't control HIV replication. Furthermore, in this study, CD4+ cell counts did not increase but CD8+ cell counts increased dramatically. Also, it's unclear if IL-2 added anything to this picture, as studies of strategic therapy interruption without IL-2 have sometimes shown similar results. For more information on Strategic Therapy Interruptions, call Project Inform's National HIV/AIDS Treatment Hotline.
On the basis of a 72-person study conducted in Europe, the French government approved IL-2 for Compassionate Use in people with CD4+ cell counts below 200 with controlled viral replication (HIV RNA below 1,000 copies/ml). The French Compassionate Use system is similar to an accelerated approval in the United States, with restrictions on who has access to the therapy.
This approval is based on results from a study of people with CD4+ cell counts between 50 and 200 and HIV RNA levels below 1,000 copies/ml who received anti-HIV therapy alone or in combination with IL-2. IL-2 was administered through injection directly under the skin (subcutaneously), twice daily for five days, every six weeks. The dose was 4.5 million international units (MIU), for a total daily dose of nine MIU. At the end of six months, people receiving IL-2 experienced a CD4+ cell count increase of 65, whereas those who only received anti-HIV therapy realized a small cell count increase of 18. Viral load was similar in the two groups. French authorities apparently concluded that the greater increase in CD4+ counts seen in the people treated with IL-2 warranted making the drug available to people with very low CD4+ levels. The study, however, did not follow the patients long enough to know whether those with increased CD4+ counts actually lived longer or had greater freedom from opportunistic infections. A much larger international study, described below, attempts to answer this question.
A 4,000-person study of IL-2, called ESPRIT, officially launched in January 2000. Volunteers receive either IL-2 by injection directly under the skin, twice daily, for five consecutive days every eight weeks, or no IL-2 therapy. The study will last for five years. Volunteers must have CD4+ cell counts above 300 to be eligible.
A second study, called SILCAAT, is open to people with CD4+ cell counts below 300 and HIV RNA levels below 10,000 copies/ml. A third study, evaluating the use of very low doses of IL-2, given daily in people with low CD4+ cell counts, is fully enrolled and expected to report data shortly. Rumor has it, however, that the low dose approach did not result in substantial increases in CD4+ cell counts.
For more information about IL-2, read Project Inform's Interleukin-2 Fact Sheet. For more information about these studies, call 1-800-TRIALS-A.
Back to the Project Inform Perspective April 2000 contents page.