FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

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

	Full Text PDF Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

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.

Full Text of this Article

Related Letters:

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

This article has been cited by other articles:

• The INSIGHT-ESPRIT Study Group and SILCAAT Scienti, (2009). Interleukin-2 Therapy in Patients with HIV Infection. NEJM 361: 1548-1559 [Abstract] [Full Text]  
• Jones, R. B., Yue, F.-Y., Gu, X. X. J., Hunter, D. V., Mujib, S., Gyenes, G., Mason, R. D., Mohamed, R., MacDonald, K. S., Kovacs, C., Ostrowski, M. A. (2009). Human Immunodeficiency Virus Type 1 Escapes from Interleukin-2-Producing CD4+ T-Cell Responses without High-Frequency Fixation of Mutations. J. Virol. 83: 8722-8732 [Abstract] [Full Text]  
• Belda, A, Borras-Blasco, J, Lopez-Montes, L, Rosique-Robles, D, Castera, E, Abad, J (2009). Foot ischaemia and toe skin necrosis associated with interleukin-2 infusion in an HIV-infected patient. Int J STD AIDS 20: 577-579 [Abstract] [Full Text]  
• Radbruch, L., Strasser, F., Elsner, F., Goncalves, J. F., Loge, J., Kaasa, S., Nauck, F., Stone, P., the Research Steering Committee of the European As, (2008). Fatigue in palliative care patients -- an EAPC approach. Palliat Med 22: 13-32 [Abstract]  
• Wei, S., Kryczek, I., Edwards, R. P., Zou, L., Szeliga, W., Banerjee, M., Cost, M., Cheng, P., Chang, A., Redman, B., Herberman, R. B., Zou, W. (2007). Interleukin-2 Administration Alters the CD4+FOXP3+ T-Cell Pool and Tumor Trafficking in Patients with Ovarian Carcinoma. Cancer Res. 67: 7487-7494 [Abstract] [Full Text]  
• Crotti, A., Lusic, M., Lupo, R., Lievens, P. M. J., Liboi, E., Chiara, G. D., Tinelli, M., Lazzarin, A., Patterson, B. K., Giacca, M., Bovolenta, C., Poli, G. (2007). Naturally occurring C-terminally truncated STAT5 is a negative regulator of HIV-1 expression. Blood 109: 5380-5389 [Abstract] [Full Text]  
• Mitsuyasu, R., Gelman, R., Cherng, D. W., Landay, A., Fahey, J., Reichman, R., Erice, A., Bucy, R. P., Kilby, J. M., Lederman, M. M., Hamilton, C. D., Lertora, J., White, B. L., Tebas, P., Duliege, A.-M., Pollard, R. B., for the AIDS Clinical Trials Group 328 Study Team, (2007). The Virologic, Immunologic, and Clinical Effects of Interleukin 2 With Potent Antiretroviral Therapy in Patients With Moderately Advanced Human Immunodeficiency Virus Infection: A Randomized Controlled Clinical Trial--AIDS Clinical Trials Group 328. Arch Intern Med 167: 597-605 [Abstract] [Full Text]  
• Vassena, L., Proschan, M., Fauci, A. S., Lusso, P. (2007). Interleukin 7 reduces the levels of spontaneous apoptosis in CD4+ and CD8+ T cells from HIV-1-infected individuals. Proc. Natl. Acad. Sci. USA 104: 2355-2360 [Abstract] [Full Text]  
• Henry, W. K., Tebas, P., Lane, H. C. (2006). Explaining, predicting, and treating HIV-associated CD4 cell loss: after 25 years still a puzzle.. JAMA 296: 1523-1525 [Full Text]  
• Brann, T. W., Dewar, R. L., Jiang, M.-K., Shah, A., Nagashima, K., Metcalf, J. A., Falloon, J., Lane, H. C., Imamichi, T. (2006). Functional Correlation between a Novel Amino Acid Insertion at Codon 19 in the Protease of Human Immunodeficiency Virus Type 1 and Polymorphism in the p1/p6 Gag Cleavage Site in Drug Resistance and Replication Fitness.. J. Virol. 80: 6136-6145 [Abstract] [Full Text]  
• Moll, M., Snyder-Cappione, J., Spotts, G., Hecht, F. M., Sandberg, J. K., Nixon, D. F. (2006). Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2. Blood 107: 3081-3083 [Abstract] [Full Text]  
• Grabar, S., Weiss, L., Costagliola, D. (2006). HIV infection in older patients in the HAART era. J Antimicrob Chemother 57: 4-7 [Abstract] [Full Text]  
• Knoechel, B., Lohr, J., Kahn, E., Bluestone, J. A., Abbas, A. K. (2005). Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. JEM 202: 1375-1386 [Abstract] [Full Text]  
• Gesbert, F., Moreau, J.-L., Theze, J. (2005). IL-2 Responsiveness of CD4 and CD8 lymphocytes: further investigations with human IL-2R{beta} transgenic mice. Int Immunol 17: 1093-1102 [Abstract] [Full Text]  
• Marchetti, G., Franzetti, F., Gori, A. (2005). Partial immune reconstitution following highly active antiretroviral therapy: can adjuvant interleukin-2 fill the gap?. J Antimicrob Chemother 55: 401-409 [Abstract] [Full Text]  
• Paiardini, M., Cervasi, B., Albrecht, H., Muthukumar, A., Dunham, R., Gordon, S., Radziewicz, H., Piedimonte, G., Magnani, M., Montroni, M., Kaech, S. M., Weintrob, A., Altman, J. D., Sodora, D. L., Feinberg, M. B., Silvestri, G. (2005). Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals. J. Immunol. 174: 2900-2909 [Abstract] [Full Text]  
• Nacsa, J., Edghill-Smith, Y., Tsai, W.-P., Venzon, D., Tryniszewska, E., Hryniewicz, A., Moniuszko, M., Kinter, A., Smith, K. A., Franchini, G. (2005). Contrasting Effects of Low-Dose IL-2 on Vaccine-Boosted Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cells in Macaques Chronically Infected with SIVmac251. J. Immunol. 174: 1913-1921 [Abstract] [Full Text]  
• Teague, R. M., Tempero, R. M., Thomas, S., Murali-Krishna, K., Nelson, B. H. (2004). Proliferation and Differentiation of CD8+ T Cells in the Absence of IL-2/15 Receptor {beta}-Chain Expression or STAT5 Activation. J. Immunol. 173: 3131-3139 [Abstract] [Full Text]  
• Sereti, I., Anthony, K. B., Martinez-Wilson, H., Lempicki, R., Adelsberger, J., Metcalf, J. A., Hallahan, C. W., Follmann, D., Davey, R. T., Kovacs, J. A., Lane, H. C. (2004). IL-2-induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation. Blood 104: 775-780 [Abstract] [Full Text]  
• Sutton, M. Y., Holland, B., Denny, T. N., Garcia, A., Garcia, Z., Stein, D., Bardeguez, A. D. (2004). Effect of Pregnancy and Human Immunodeficiency Virus Infection on Intracellular Interleukin-2 Production Patterns. CVI 11: 780-785 [Abstract] [Full Text]  
• Farel, C. E., Chaitt, D. G., Hahn, B. K., Tavel, J. A., Kovacs, J. A., Polis, M. A., Masur, H., Follmann, D. A., Lane, H. C., Davey, R. T. Jr (2004). Induction and maintenance therapy with intermittent interleukin-2 in HIV-1 infection. Blood 103: 3282-3286 [Abstract] [Full Text]  
• Sereti, I., Martinez-Wilson, H., Metcalf, J. A., Baseler, M. W., Hallahan, C. W., Hahn, B., Hengel, R. L., Davey, R. T., Kovacs, J. A., Lane, H. C. (2002). Long-term effects of intermittent interleukin 2 therapy in patients with HIV infection: characterization of a novel subset of CD4+/CD25+ T cells. Blood 100: 2159-2167 [Abstract] [Full Text]  
• Natarajan, V., Lempicki, R. A., Sereti, I., Badralmaa, Y., Adelsberger, J. W., Metcalf, J. A., Prieto, D. A., Stevens, R., Baseler, M. W., Kovacs, J. A., Lane, H. C. (2002). Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection. Proc. Natl. Acad. Sci. USA 99: 10712-10717 [Abstract] [Full Text]  
• Otieno, M. W., Banura, C., Katongole-Mbidde, E., Johnson, J. L., Ghannoum, M., Dowlati, A., Renne, R., Arts, E., Whalen, C., Lederman, M. M., Remick, S. C. (2002). Therapeutic Challenges of AIDS-Related Non-Hodgkin's Lymphoma in the United States and East Africa. JNCI J Natl Cancer Inst 94: 718-732 [Abstract] [Full Text]  
• Schrager, J. A., Der Minassian, V., Marsh, J. W. (2002). HIV Nef Increases T Cell ERK MAP Kinase Activity. J. Biol. Chem. 277: 6137-6142 [Abstract] [Full Text]  
• Paiardini, M., Galati, D., Cervasi, B., Cannavo, G., Galluzzi, L., Montroni, M., Guetard, D., Magnani, M., Piedimonte, G., Silvestri, G. (2001). Exogenous Interleukin-2 Administration Corrects the Cell Cycle Perturbation of Lymphocytes from Human Immunodeficiency Virus-Infected Individuals. J. Virol. 75: 10843-10855 [Abstract] [Full Text]  
• Lieberman, J., Shankar, P., Manjunath, N., Andersson, J. (2001). Dressed to kill? A review of why antiviral CD8 T lymphocytes fail to prevent progressive immunodeficiency in HIV-1 infection. Blood 98: 1667-1677 [Abstract] [Full Text]  
• Bender, M. A., Sax, P. E., Le Moal, G., Breux, J.-P., Roblot, F., Lopez Bernaldo de Quiros, J. C., Miro, J. M., Pena, J. M., Lundgren, J., Reiss, P., Ledergerber, B. (2001). Discontinuing Prophylaxis against Pneumocystis carinii Pneumonia. NEJM 344: 1639-1641 [Full Text]  
• Collier, A. C., Kalish, L. A., Busch, M. P., Gernsheimer, T., Assmann, S. F., Lane, T. A., Asmuth, D. M., Lederman, M. M., Murphy, E. L., Kumar, P., Kelley, M., Flanigan, T. P., McMahon, D. K., Sacks, H. S., Kennedy, M. S., Holland, P. V., for the Viral Activation Transfusion Study Group, (2001). Leukocyte-Reduced Red Blood Cell Transfusions in Patients With Anemia and Human Immunodeficiency Virus Infection: The Viral Activation Transfusion Study: A Randomized Controlled Trial. JAMA 285: 1592-1601 [Abstract] [Full Text]  
• Ansari, A. F., Etzel, J. V. (2000). Immune-Based Therapies for the Management of HIV Infection: Highly Active Antiretroviral Therapy and Beyond. Journal of Pharmacy Practice 13: 515-532 [Abstract]  
• Mitsuyasu, R. T., Anton, P. A., Deeks, S. G., Scadden, D. T., Connick, E., Downs, M. T., Bakker, A., Roberts, M. R., June, C. H., Jalali, S., Lin, A. A., Pennathur-Das, R., Hege, K. M. (2000). Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4+ and CD8+ T cells in human immunodeficiency virus-infected subjects. Blood 96: 785-793 [Abstract] [Full Text]  
• Walker, R. E., Bechtel, C. M., Natarajan, V., Baseler, M., Hege, K. M., Metcalf, J. A., Stevens, R., Hazen, A., Blaese, R. M., Chen, C. C., Leitman, S. F., Palensky, J., Wittes, J., Davey, R. T. Jr, Falloon, J., Polis, M. A., Kovacs, J. A., Broad, D. F., Levine, B. L., Roberts, M. R., Masur, H., Lane, H. C. (2000). Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood 96: 467-474 [Abstract] [Full Text]  
• Davey, R. T. Jr, Murphy, R. L., Graziano, F. M., Boswell, S. L., Pavia, A. T., Cancio, M., Nadler, J. P., Chaitt, D. G., Dewar, R. L., Sahner, D. K., Duliege, A.-M., Capra, W. B., Leong, W.-P., Giedlin, M. A., Lane, H. C., Kahn, J. O. (2000). Immunologic and Virologic Effects of Subcutaneous Interleukin 2 in Combination With Antiretroviral Therapy: A Randomized Controlled Trial. JAMA 284: 183-189 [Abstract] [Full Text]  
• Blankson, J., Siliciano, R. F. (2000). Interleukin 2 Treatment for HIV Infection. JAMA 284: 236-238 [Full Text]  
• Tateyama, M., Oyaizu, N., McCloskey, T. W., Than, S., Pahwa, S. (2000). CD4 T lymphocytes are primed to express Fas ligand by CD4 cross-linking and to contribute to CD8 T-cell apoptosis via Fas/FasL death signaling pathway. Blood 96: 195-202 [Abstract] [Full Text]  
• Fallon, E. M., Liparoto, S. F., Lee, K. J., Ciardelli, T. L., Lauffenburger, D. A. (2000). Increased Endosomal Sorting of Ligand to Recycling Enhances Potency of an Interleukin-2 Analog. J. Biol. Chem. 275: 6790-6797 [Abstract] [Full Text]  
• Bovolenta, C., Camorali, L., Lorini, A. L., Vallanti, G., Ghezzi, S., Tambussi, G., Lazzarin, A., Poli, G. (1999). In Vivo Administration of Recombinant IL-2 to Individuals Infected by HIV Down-Modulates the Binding and Expression of the Transcription Factors Ying-Yang-1 and Leader Binding Protein-1/Late Simian Virus 40 Factor. J. Immunol. 163: 6892-6897 [Abstract] [Full Text]  
• Pyeon, D., Splitter, G. A. (1999). Regulation of Bovine Leukemia Virus tax and pol mRNA Levels by Interleukin-2 and -10. J. Virol. 73: 8427-8434 [Abstract] [Full Text]  
• Chun, T.-W., Fauci, A. S. (1999). Latent reservoirs of HIV: Obstacles to the eradication of virus. Proc. Natl. Acad. Sci. USA 96: 10958-10961 [Full Text]  
• M. McKinney, D., Lewinsohn, D. A., Riddell, S. R., Greenberg, P. D., Mosier, D. E. (1999). The Antiviral Activity of HIV-Specific CD8+ CTL Clones Is Limited by Elimination Due to Encounter with HIV-Infected Targets. J. Immunol. 163: 861-867 [Abstract] [Full Text]  
• Sousa, A. E., Chaves, A. F., Doroana, M., Antunes, F., Victorino, R. M. M. (1999). Kinetics of the Changes of Lymphocyte Subsets Defined by Cytokine Production at Single Cell Level During Highly Active Antiretroviral Therapy for HIV-1 Infection. J. Immunol. 162: 3718-3726 [Abstract] [Full Text]  
• David, D., Bani, L., Moreau, J.-L., Treilhou, M.-P., Nakarai, T., Joussemet, M., Ritz, J., Dupont, B., Pialoux, G., Theze, J. (1998). Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy. Proc. Natl. Acad. Sci. USA 95: 11348-11353 [Abstract] [Full Text]  
• Fahey, J. L. (1998). Cytokines, Plasma Immune Activation Markers, and Clinically Relevant Surrogate Markers in Human Immunodeficiency Virus Infection. CVI 5: 597-603 [Full Text]  
• Barouch, D. H., Santra, S., Steenbeke, T. D., Zheng, X. X., Perry, H. C., Davies, M.-E., Freed, D. C., Craiu, A., Strom, T. B., Shiver, J. W., Letvin, N. L. (1998). Augmentation and Suppression of Immune Responses to an HIV-1 DNA Vaccine by Plasmid Cytokine/Ig Administration. J. Immunol. 161: 1875-1882 [Abstract] [Full Text]  
• Xi, S., Cohen, D., Chen, L. H. (1998). Effects of fish oil on cytokines and immune functions of mice with murine AIDS. J. Lipid Res. 39: 1677-1687 [Abstract] [Full Text]  
• Schrager, L. K., D'Souza, M. P. (1998). Cellular and Anatomical Reservoirs of HIV-1 in Patients Receiving Potent Antiretroviral Combination Therapy. JAMA 280: 67-71 [Abstract] [Full Text]  
• Ledru, E., Lecoeur, H., Garcia, S., Debord, T., Gougeon, M.-L. (1998). Differential Susceptibility to Activation-Induced Apoptosis Among Peripheral Th1 Subsets: Correlation with Bcl-2 Expression and Consequences for AIDS Pathogenesis. J. Immunol. 160: 3194-3206 [Abstract] [Full Text]  
• Parada, N. A., Center, D. M., Kornfeld, H., Rodriguez, W. L., Cook, J., Vallen, M., Cruikshank, W. W. (1998). Synergistic Activation of CD4+ T Cells by IL-16 and IL-2. J. Immunol. 160: 2115-2120 [Abstract] [Full Text]  
• David, D., Bani, L., Moreau, J.-L., Demaison, C., Sun, K., Salvucci, O., Nakarai, T., de Montalembert, M., Chouaib, S., Joussemet, M., Ritz, J., Theze, J. (1998). Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets. Blood 91: 165-172 [Abstract] [Full Text]  
• Ballow, M., Nelson, R. (1997). Immunopharmacology: Immunomodulation and Immunotherapy. JAMA 278: 2008-2017 [Abstract]  
• Abstract and Commentary, , Landay, A. L. (1997). Immune Restoration Following Treatment. JAMA 278: 1538-1538 [Abstract]  
• Hashimoto, F., Oyaizu, N., Kalyanaraman, V. S., Pahwa, S. (1997). Modulation of Bcl-2 Protein by CD4 Cross-Linking: A Possible Mechanism for Lymphocyte Apoptosis in Human Immunodeficiency Virus Infection and for Rescue of Apoptosis by Interleukin-2. Blood 90: 745-753 [Abstract] [Full Text]  
• Jacobson, E. L., Pilaro, F., Smith, K. A., Kovacs, J. A., Davey, R. T., Lane, H. C. (1997). Interleukin-2 Infusions in HIV-Infected Patients. NEJM 336: 1260-1261 [Full Text]  
• (1996). Interleukin-2 for HIV. AIDS Clin Care 1996: 6-6 [Full Text]  
• (1996). IL-2 RAISES CD4 COUNTS IN HIV INFECTION. JWatch General 1996: 3-3 [Full Text]