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Previous Volume 335:1350-1356 October 31, 1996 Number 18 Next

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ABSTRACT

Background Interleukin-2 is a cytokine that regulates the proliferation and differentiation of lymphocytes. In preliminary studies, intermittent infusions of interleukin-2 led to increases in CD4 counts in patients with human immunodeficiency virus (HIV) infection and more than 200 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 CD4 counts above 200 cells per cubic millimeter were randomly assigned to receive either interleukin-2 plus antiretroviral therapy (31 patients, 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 day. Safety and immunologic and virologic measures were monitored monthly until four months after the last treatment cycle.

Results In patients treated with interleukin-2, the mean (±SE) CD4 count increased from 428±25 cells per cubic millimeter at base line to 916±128 at month 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 months 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 infection and base-line CD4 counts above 200 cells per cubic millimeter, intermittent infusions of interleukin-2 produced substantial and sustained increases in CD4 counts with no associated increase in plasma HIV RNA levels.

Source Information

From the Critical Care Medicine Department, Clinical Center (J.A.K.), the Laboratory of Immunoregulation (S.V., J.F., R.T.D., R.E.W., M.A.P., K.S., J.A.M., H.C.L.), and the Division of AIDS (J.M.A.), National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Science Applications International Corporation, Frederick, Md. (M.B.); and Chiron Corporation, Emeryville, Calif. (G.F.). Other authors were Robin J. Dewar, Ph.D., Science Applications International Corporation, Frederick, Md.; and Henry Masur, M.D., Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Md.The U.S. government has been issued a patent for immunologic enhancement with intermittent interleukin-2 therapy, listing Drs. Kovacs and Lane as inventors.

Address reprint requests to Dr. Kovacs at Bldg. 10, Rm. 7D43, MSC 1662, National Institutes of Health, Bethesda, MD 20892-1662.

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Interleukin-2 Infusions in HIV-Infected Patients
Jacobson E. L., Pilaro F., Smith K. A., Kovacs J. A., Davey R. T., Lane H. C.
Extract | Full Text  
N Engl J Med 1997; 336:1260-1261, Apr 24, 1997. Correspondence

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