Summary
We have investigated the effects of combination therapy with thymosin α1 and natural human lymphoblastoid interferon-α in human immunodeficiency virus infection and have shown that in vitro this combination treatment: (1) synergistically stimulated the cytotoxic activity against natural killer-sensitive target cells of lymphocytes collected from human immunodeficiency virus-infected donors and (2) did not interfere with the antiviral activity of zidovudine. We thus studied the effects of combination therapy with thymosin α1, interferon-α and zidovudine in patients with CD4+ lymphocytes ranging from 200 to 500/mm3 in a randomized non-blinded study and found that the treatment was well tolerated after 12 months of therapy and was associated with a substantial increase in the number and function of CD4+T cells. A similar effect was not observed in human immunodeficiency virus patients treated with zidovudine alone or associated with single agents. These data suggest the need for a controlled, double-blind clinical trial, recently initiated with the approval and the support of the Italian Ministry of Health.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ameisen JC, Capron A, Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol Today 12:102, 1991
Bonovida B, Katz J, Gottlieb M, Mechanism, of defective NK cell activity in patients with acquired immunodeficiency syndrome (AIDS) AIDS-related complex. J Immunol 137:1157, 1986.
Boucher CA, O'Sullivan E, Mulder JW, et al, Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects. J Infect Dis 165:105, 1992
DiMacco E, Aebischer ML, Angeloni U, et al, Towards a PCR test for HIV screening of blood donors (abstract). Abstracts of the VIII International Conference on AIDS, Amsterdam, 19–24 July 1992. Congrex Holland, Amsterdam, p 315, 992
Fauci AC, The human immunodeficiency virus: infectivity and mechanism of pathogenesis. Science 239:617, 1988
Favalli C, Jezzi T, Mastino A, et al, Modulation of natural killer activity by thymosin alpha 1 and interferon. Cancer Immunol Immunother 20:189, 1985
Favalli C, Mastino A, Jezzi T, et al, Synergistic effect of thymosin alpha 1 and alpha-beta interferon on NK activity in tumor-bearing mice. Int J Immunopharmacol 11:443, 1989.
Favalli C, Mastino A, Grelli S, et al, Rationale for therapeutic approaches with thymosin α1, interleukin 2 and inteferferon in combination with chemotherapy. In: Goldstein AL, Garaci E (eds) Combination therapies. Plenum, New York, pp 275–281, 1992
Fischl MA, Richman DD, Grieco MH, et al, The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS related complex: a double-blind, placebo controlled trial. N Engl J Med 317:185, 1987
Garaci E, Mastino A, Favalli C, Enhanced immune response and antitumor immunity with combinations of biological response modifiers. Bull NY Acad Med 65:111, 1989
Garaci E, Mastino A, Pica F, et al, Combination treatment using thymosin α1 and interferon after cyclophosphamide is able to cure Lewis lung carcinoma in mice. Cancer Immunol Immunother 32:154, 1990
Garaci E, Pica F, Mastino A, et al, Antitumor effect of thymosin α1/interleukin-2 or thymosin α1 interferon α, β following cyclophosphamide in mice injected with highly metastatic Fried erythroleukemia cells. J Immunother 13:7, 1993
Graham NM, Zeger SL, Park LP, et al, The effects on survival of early treatment of human immunodeficiency virus infection. N Engl J Med 326:1037, 1992
Herberman RB, Nunn ME, Lavrin DH, Natural cytotoxic reactivity of mouse lymphoid cells against syngenic and allogenic tumors. I. Distribution of reactivity and specificity. Int J Cancer 16:216, 1975
Lane CL, Davey V, Kovacs JA, et al, Interferon α in patients with asymptomatic human immunodeficiency virus (HIV) infection. Ann Intern Med 112:805, 1990
Larder BA, Kelliam P, Kemp SD, Zidovudine resistance predicted by direct detection of mutation in DNA from HIV-infected lymphocytes. AIDS 5:137, 1991
Larder BA, Coates KE, Kemp SD, Zivovudine-resistant human immunodeficiency virus selected by passage in cell culture. J Virol 65:5232, 1991
Lucey DR, Melcher GP, Hendrix CW, et al, Human immuno-deficiency virus infection in the US Air Force: seroconversion assay to predict change in CD4+ T cell counts. J Infect Dis 164:631, 1991
Murray HW, Rubbin BY, Masur H, et al, Imparied production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med 310:883, 1988
Quinti I, Palma C, Guerra EC, et al, Proliferative and cytotoxic responses to mannoproteins ofCandida, albicans by peripheral blood lymphocytes of HIV-infected subjects. Clin Exp Immunol 85:485, 1991.
Shearer GM, Clerici M, Early T-helper cell defects in HIV-1 infection. AIDS 5:245, 1991
Shearer GM, Clerici M, How human immunodeficiency virus ravages the immune system. Curr Opin Immunol 4:463, 1992
Via CS, Shearer GM, Autoimmunity and the acquired immune deficiency syndrome. Curr Opin Immunol 1:753, 1989
Yarchoan R, Mitsuya H, Broder S. The immunology of HIV infection: implications for therapy. AIDS Res Hum Retroviruses 8:1023, 1992
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Garaci, E., Rocchi, G., Perroni, L. et al. Combination treatment with zidovudine, thymosin α1 and interferon-α in human immunodeficiency virus infectionand interferon-α in human immunodeficiency virus infection. Int J Clin Lab Res 24, 23–28 (1994). https://doi.org/10.1007/BF02592405
Issue Date:
DOI: https://doi.org/10.1007/BF02592405