CONTROLLED TRIAL OF INTERLEUKIN-2 INFUSIONS IN PATIENTS INFECTED WITHTHE HUMAN-IMMUNODEFICIENCY-VIRUS

Background Interleukin-2 is a cytokine that regulates the proliferatio n and differentiation of lymphocytes. In preliminary studies, intermit tent infusions of interleukin-2 led to increases in CD4 counts in pati ents with human immunodeficiency virus (HIV) infection and more than 2 00 CD4 cells per cubic millimeter. We conducted a controlled study to evaluate the long-term effects of such therapy on both CD4 counts and the viral burden. Methods Sixty HIV-infected patients with base-line C D4 counts above 200 cells per cubic millimeter were randomly assigned to receive either interleukin-2 plus antiretroviral therapy (31 patien ts, 1 of whom was lost to follow-up) or antiretroviral therapy alone ( 29 patients). Interleukin-2 was administered every two months for six cycles of five days each, starting at a dosage of 18 million IU per da y. Safety and immunologic and virologic measures were monitored monthl y until four months after the last treatment cycle. Results In patient s treated with interleukin-2, the mean (+/-SE) CD4 count increased fro m 428+/-25 cells per cubic millimeter at base line to 916+/-128 at mon th 12, whereas in the control group, the mean CD4 count decreased from 406+/-29 cells per cubic millimeter to 349+/-41 (P<0.001). There were no significant differences between the groups in serial measurements of the plasma HIV RNA or p24 antigen concentration during the 12 month s of treatment. Constitutional symptoms (fever, malaise, and fatigue) and asymptomatic hyperbilirubinemia were the chief dose-limiting toxic effects of interleukin-2 therapy. Conclusions In patients with HIV in fection and base-line CD4 counts above 200 cells per cubic millimeter, intermittent infusions of interleukin-2 produced substantial and sust ained increases in CD4 counts with no associated increase in plasma HI V RNA levels. (C) 1996, Massachusetts Medical Society.