A recent study showed that interleukin-2 (IL-2), a signaling molecule that stimulates growth of disease-fighting blood cells in the immune system, induces a significant increase in the number of CD4 immune cells during early HIV infection of patients.

However, IL-2 therapy was associated with a higher rate of opportunistic infections, which take advantage of weaknesses in the immune system, and death compared to no treatment. The study was published in the journal PLoS One.

The addition of short courses of antiretroviral therapy (ART) to the IL-2 treatment did not further increase the number of CD4 cells compared to IL-2 alone.

ART, a combination of at least three antiviral drugs, is designed to suppress and stop the progression of HIV infection. However, it does not completely eradicate the HIV virus, and once started, the treatment must be continued for life, since interruptions or discontinuation can increase risk of disease progression or death.

The purpose of the study, known as STALWART, was to investigate whether IL-2 alone or in combination with short courses of ART would enhance immunologic response without the adverse effects of continuous ART.

The study evaluated the safety and efficacy of IL-2 in 267 patients not yet ready for continuous ART.

Participants received either no treatment, IL-2 for five consecutive days every eight weeks for three cycles, or the same IL-2 regimen with the addition of ten days of ART administered around each IL-2 cycle.

At week 32 of the study, the mean change in CD4 cells in participants not receiving treatment was -22 cells/mm³ compared to a change of +114 for IL-2 recipients. Participants receiving IL-2 plus ART showed a similar increase in CD4 cells to those receiving IL-2 alone.

Increased CD4 counts in IL-2 patients delayed the start of continuous ART. However, the amount of HIV virus in the blood stream was unaffected by treatment with IL-2.

Despite the potential benefits of IL-2, treatment with the drug was associated with increased side effects, opportunistic infections, and progression to AIDS or death, which calls into question the potential of IL-2-induced CD4 cells to fight disease.

Patients receiving IL-2 were more than twice as likely to develop moderate or severe side effects as patients receiving no therapy, and those receiving ART in addition to IL-2 were more than four times as likely. Common side effects included fever, nausea, muscle pain, and rash.

Overall, researchers believe that IL-2 might be an effective strategy to complement ART, rather than to replace it.

They also concluded that CD4 counts might not be the best way of measuring immune function in IL-2 recipients, since the efficacy of IL-2 induced CD4 cells is uncertain. Instead, researchers suggest it might be useful to differentiate IL-2 induced cells to more accurately measure disease progression in patients who have received IL-2.

To extend safety evaluations, participants in the study will be offered an additional two years of clinical follow-up.

Two other studies (ESPRIT and SILCAAT), designed to evaluate the clinical efficacy of intermittent IL-2 plus continuous ART compared to ART alone, also concluded that the addition of IL-2 did not slow disease progression or prevent death compared to ART alone, despite increased CD4 cells.

Another clinical trial (ANRS 119) compared IL-2 therapy alone to no intervention and found that IL-2 recipients delayed ART initiation compared to controls and did not experience increased clinical events.

“We currently have no plans to carry out new studies with IL-2. However, other [signaling molecules] like IL-7, which are better tolerated, might be more interesting to assess,” said Jean-Michel Molina, principle investigator of the ANRS 119 study.

For more information regarding the STALWART study, please see the article in PLoS One.