Immunologic and Virologic Effects of Subcutaneous Interleukin 2 in Combination with Antiretroviral Therapy: A Randomized Controlled Trial [Davey RT, Jr, et al. JAMA 2000; 284: 183]: This is a controlled trial in 82 participants comparing immunologic and virologic outcome with HAART therapy alone compared to HAART therapy plus IL-2. Participants had CD4 cell counts at baseline at 200 - 500 cells/mm3 and viral levels <10,000 copies/mL. The IL-2 recipients received 5-day courses separated by eight weeks using 7.5 mIU twice daily. The results are summarized in the table below for viral load, increases in CD4 count, and adverse effects:
| Results of IL-2 Trial |
| |
IL-2 + HAART |
HAART alone |
| VL <50 copies/mL at 1 yr. |
20/28 (71%) |
13/30 (43%)* |
| Increase in CD4 cell count |
112% |
18%* |
| Adverse effects |
54% |
16%* |
| * p <0.05 |
Comment: IL-2 is a polypeptide hormone produced by activated T-cells that stimulates production of antigen-activated T-cells. There are three potential benefits in HIV-infected patients: 1) IL-2 increases the CD4 cell count to counteract the HIV-induced loss; 2) it serves as a growth factor for CD8 cytolytic T-cells that are important components of the immune response to HIV; and 3) some have suggested that it may purge the reservoir of latently infected CD4 cells to make them vulnerable to antiretroviral therapy. The study by Davey, et al. is highly encouraging, but does have important limitations. First, it is not clear that this benefit in the CD4 rebound will translate into clinical benefit. More concerning are the side effects associated with IL-2. The major toxicities are fever, fatigue and myalgias, which can often be managed with acetaminophen and ibuprofen, and sometimes oral narcotics to control rigors. In this study the more serious or sustained symptoms were managed by omitting a dose, reducing the dose, or doing both. One of these was required in 54% of the IL-2 recipients. It is possible that lower doses of IL-2 could be used. There is also concern that the patients who need IL-2 the most, those with CD4 cell counts <200/mm3, were excluded from this trial as well as most others using IL-2. A preliminary report suggests that there may be benefit in patients with low CD4 counts as well [JID 1999; 180: 56]. The final concern is cost since the AWP for IL-2 is $640/22 mIU, and there are also infusion costs. This will not be a substitute for another expensive drug, which is what we have encountered with new antiretroviral agents, but it will be a cost that is added to HAART, which is already $10 - 12,000/year.
posted 7/19/2000
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