Interleukin-2 (IL-2, Proleukin)

March 2007     View PDF     En español

What does the research show?

Researchers have experi­mented with 3 ways to give IL-2: injection under the skin (subcutaneous, or subQ), injection in the stomach muscles, and infusion into a vein (intravenous or IV). They have tried different schedules—daily, weekly, monthly and every 2 months. They have also experimented with different doses, from very low daily doses (1 million International Units, or IU) to higher intermittent doses (18 million IU).

Experimental formulas of IL-2 have been tried and more are being studied. Large studies are underway to evaluate a cycled strategy of twice a day subQ IL-2 injections, at doses of 9 MIU (4.5 twice a day) or 15 MIU (7.5 twice a day), for 5 consecutive days, every 2 months. This approach is effective in producing large increases in the number of CD4+ cells. Increases of 100–400 or more CD4+ cells have been routinely achieved, beyond the improvements seen from standard anti-HIV therapies.

In lab research, IL-2 is often used to stimulate HIV-infected cells to reproduce. When IL-2 is used this way, it causes the infected cells to produce large amounts of new HIV particles. Because of this, some researchers feared using the drug in humans, where they certainly don’t want to see increased production of HIV. However, these fears have not been seen in studies.

To the contrary, changes in HIV levels are similar among groups taking IL-2 together with anti-HIV therapy compared to those on anti-HIV therapy alone. After a course of IL-2, there is often a burst of HIV activity, but it’s not sustained and there’s no evidence that these temporary elevations in HIV levels cause harm. Nonetheless, this concern causes most researchers to use IL-2 only in people using anti-HIV therapies.

Researchers tailor IL-2 dosing and scheduling to fit the individual’s needs—trying to optimize CD4+ cell count increases and minimize side effects. If side effects occur, doses are reduced and/or courses are shortened to improve tolerability. If CD4+ cell counts rise to normal ranges, therapy is given less often to maintain those increases. So far in studies, people who started IL-2 therapy while CD4+ cell counts were high (above 400) generally had more immediate and pronounced increases in CD4+ cell counts, resulting in the need for less frequent IL-2 therapy.

One study at the National Institutes of Health included people with CD4+ cell counts around 600. Within the first three cycles, IL-2 recipients experienced CD4+ cell count increases to about 1,200. The average time between cycles that kept CD4+ cell counts at this level was about one year. However, if CD4+ cell counts are below 300 when IL-2 is started, then CD4+ cell count increases are usually less immediate and pronounced. Therefore, to maintain ideal CD4+ cell counts in such people, a much longer time on bi-monthly IL-2 cycles may be required before the period between cycles can be extended.

Using IL-2 as part of structured treatment inter­ruptions (STIs) has also received attention. This is discussed briefly in Project Inform’s publication, Strategies for Attempting Structured Therapy Interruptions.

A few completed studies looked at using IL-2 as part of an eradication strategy. So far, they have not shown that completely removing HIV from a person’s body is possible—with or without IL-2.

Studies of low dose daily injections of IL-2 have not resulted in the dramatic CD4+ cell increases seen with the higher dose cycle, although this approach may cause fewer side effects. Following less than remarkable results from a moderately sized study, the company developing IL-2 at that time (Chiron Corporation) stopped major development efforts on low dose IL-2. Nonetheless, some individuals and doctors still experiment with this approach, hoping to find an ideal balance between potential benefits and known side effects.

Finally, a moderate size study in people with very low CD4+ cell counts (below 200) and controlled HIV repli­cation (below 1,000 copies HIV RNA) showed that IL-2 therapy could lead to modest increases in CD4+ cell counts. Results have led the French regulatory agency to approve a Compassionate Use Program for IL-2 for people with low CD4+ cell counts and HIV levels below 1,000. These data, combined with other study results, provided French authorities with enough confidence to make IL-2 more widely available to people with more advanced-stage HIV disease. The FDA in the US has taken a more conservative approach and has not approved access to IL-2 in the same way. Despite this, some people in the US manage to get IL-2; since once a drug is approved by the FDA, doctors have the right to use it however they choose. However, private insurance and other payers may not be willing to pay for the drug.

Introduction

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