HIV-positive patients taking interleukin-2 (Proleukin) alongside antiretroviral therapy experience problems that reduce their quality of life, according to the results of a study presented in the 1st December edition of The Journal of Acquired Immune Deficiency Syndromes. However, these effects are transient and may be replaced by positive effects in the long term.
Interleukin-2 is a chemical that is produced naturally by the immune system. Studies have shown that injecting interleukin-2 can lead to increases in CD4 cell counts in HIV-positive patients. Although further studies are needed to determine whether these effects improve patients’ health, interleukin-2 may enable them to delay the start of antiretroviral therapy or it may enhance the effects of anti-HIV drugs.
Despite its positive effects, interleukin-2 also has a range of side-effects, including influenza-like symptoms. It can also cause irritation when it is injected under the skin. The alternative method of administration is through a line inserted into a vein.
To weigh up the positive and negative effects of interleukin-2 as patients perceive them, investigators from the Adult AIDS Clinical Trials Group (ACTG) asked 148 HIV-positive patients to complete questionnaires covering eight main areas related to their quality of life.
All of the patients took an anti-HIV drug combination of indinavir (Crixivan) and two nucleoside reverse transcriptase inhibitors (NRTIs) for twelve weeks. Then they were randomised to continue with this drug combination alone, to add subcutaneous injections of interleukin-2, or to add intravenous injection of interleukin-2.
Both interleukin-2 regimens were administered in eight-weekly cycles. Subcutaneous injections were given as 7.5MIU twice daily for five days, while intravenous injections were 9MIU daily for five days.
“We found no evidence of a long-term adverse impact of interleukin-2 administration on quality of life, despite the short-term detriments evident during treatment administration cycles,” write the investigators. “If further research determines that immunologic effects of interleukin-2 translate into clinical benefit, subcutaneous or intravenous interleukin-2 may be a reasonable treatment option for patients who are willing to tolerate its short-term side-effects.”
The investigators examined the effects of interleukin-2 on quality of life on the fifth day of three of the treatment cycles. They saw that patients receiving the drug had lower quality of life scores across all eight areas during the cycle, when compared to just before the cycle began.
The effects of subcutaneous injection were more severe than those of intravenous injection for four areas: general health, energy, mental health and social functioning, as well as for overall quality of life. “This most likely is attributable to the added discomfort of local reactions at the site of subcutaneous administration,” the investigators suggest.
The reductions in quality of life observed during the treatment cycle did not vary significantly across three cycles. “Our data do not suggest that patients adapt to the side-effects over time but, rather, that they continue to experience them as a significant detriment to quality of life,” the researchers explain.
In contrast to the drug's effects during treatment cycles, the investigators saw improved quality of life scores between cycles. When they looked at quality of life at 16 weeks after the first cycle of injections, the investigators found that the subcutaneous interleukin-2 group had significantly greater scores than the other two groups in two of the quality-of-life areas: role functioning and cognitive functioning.
Similarly, 40-week data showed a significant improvement in this group for overall quality of life (p = 0.02), as well as for three of the eight areas: physical functioning, role functioning and bodily pain.
Both interleukin-2 groups had enhanced elevations of CD4 cell count over the entire 84 week study. While patients taking antiretroviral therapy alone had a median increase of 102 cells/mm3, those receiving subcutaneous injections of interleukin-2 had a median increase of 312 cells/mm3. Patients receiving intravenous interleukin-2 had a larger increase of 459 cells/mm3 by the end of the study.
“Interestingly, the subcutaneous interleukin-2 group had the best health-related quality of life scores overall, but the intravenous group had the best immunologic measures of the three treatment groups,” the researchers write. “Health-related quality of life scores in the intravenous interleukin-2 group may have been affected by issues of inconvenience and time required for treatment, which were not specifically asked about on our questionnaires.”
Interleukin-2 is not a licensed drug for use in HIV, as further research is required to prove its effectiveness in improving the health of patients.
Martin BK et al. Quality of life in a clinical trial of highly active antiretroviral therapy alone or with intravenous or subcutaneous interleukin-2 administration. J Acquir Immune Defic Syndr 40: 428-433, 2005.