Abstract
Rationale and objective: Early long-term treatment with recombinant interferon (IFN) alpha-2b delayed disease progression in asymptomatic Human Immunodeficiency Virus (HIV) carriers in a randomized trial that lasted from October 1987 to February 1992 (14). The aim of the work reported in this paper was to observe if there was also an effect on survival when the same patients were followed-up further.
Design and interventions: IFN alpha-2b was given 3 × 106 IU, 3 times weekly. The control group did not receive any treatment. The main end-point for this evaluation was death due to any cause. The deadline was August 1995.
Population: Subjects were anti-HIV-1 seropositive, Western blot-confirmed, asymptomatic (CDC group II), or with generalized lymphadenopathies (CDC group III). The groups had 79 (control) and 83 (IFN) patients.
Main results: Mean survival was longer in the IFN group (95% CI: 127–152 vs. 101–120 months since infection or 80–90 vs. 70–82 months since the start of treatment). Survival rates were higher in IFN-treated individuals (61–77% vs. 24–54% at 10 years of infection or 53–69% vs. 34–52% at 7 years of treatment or follow-up). It was also confirmed that disease progression is significantly slower in IFN-treated patients. There were 23.4 vs. 3.2% long-term survivors in the IFN and control groups, respectively (p=0.005). IFN-treated patients had fewer AIDS-related malignancies (5 vs. 11), mainly Kaposi’s sarcomas (1 vs. 5). This difference was not statistically significant, but clinically interesting. There was no difference in survival if measured since the onset of AIDS.
Conclusion: IFN alpha treatment given from the early stages of infection, but not after the appearance of AIDS symptoms, can prolong survival.
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Abbreviations
- IFN:
-
interferon
- HIV:
-
Human Immunodeficiency Virus
- CDC:
-
Center for Disease Control (USA)
- AIDS:
-
Acquired Immune Deficiency Syndrome
- SD:
-
standard deviation
- CI:
-
Confidence Interval
References
Mulder JW, Cooper DA & Mathiesen L, et al. Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017). AIDS 1994; 8(3): 313–21.
Ragni MV, Amato DA & LoFaro ML et al. Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups. Blood 1995; 85(9): 2337–46.
Andrieu JM, Lu W & Levy R. Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year. J Infect Dis 1995; 171(3): 523–30.
Mannucci PM, Gringeri A & Savidge G et al. Randomized double-blind, placebo-controlled trial of twice-daily zidovudine in asymptomatic haemophiliacs infected with the human immunodeficiency virus type 1. Br J Haematol 1994; 86(1): 174–9.
Aboulker JP & Swart AM. Preliminary analysis of the Concorde trial. Lancet 1993; 341: 889–890.
Volberding PA, Lagakos SW & Grimes JM et al. A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. N Engl J Med 1995; 333(7): 401–7.
Volberding PA, Lagakos SW & Grimes JM et al. The duration of zidovudine benefit in persons with asymptomatic HIV infection. Prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group. J Amer Med Associat 1994; 272(6): 437–42.
Ioannidis JP, Cappelleri JC & Lau J et al. Early or deferred zidovudine therapy in HIV-infected patients without an AIDS-defining illness. Ann Intern Med 1995; 122(11): 856–66.
Lenderking WR, Gelber RD & Cotton DJ et al. Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. N Engl J Med 1994; 330(11):738–43.
Zaretsky MD. AZT toxicity and AIDS prophylaxis: is AZT beneficial for HIV+ asymptomatic persons with 500 or more T4 cells per cubic millimeter? Genetica 1995; 95(1–3): 91–101.
Pitha PM. Multiple effects of interferon on the replication of human immunodeficiency virus type 1. Antiviral Res 1994; 24(2–3): 205–19.
Francis ML, Meltzer MS & Gendelman HE. Interferons in the persistence, pathogenesis, and treatment of HIV infection. AIDS Res Human Retroviruses 1992; 8: 199–207.
Tappero JW, Conant MA, Wolfe SF & Berger TG. Kaposi’s sarcoma. Epidemiology, pathogenesis, histology, clinical spectrum, staging criteria and therapy. J Amer Acad Dermatol 1993; 28: 371–95
Rivero J, Limonta M, Aguilera A, Fraga M & Lopez-Saura P. Use of recombinant interferon-alpha in human immunodeficiency virus (HIV)-infected individuals. Biotherapy 1995; 8(1):23–31.
Revision of the CDC surveillance case definition for Acquired Immunodeficiency Syndrome. Council of State and Territorial Epidemiologist; AIDS program, Center for Infectious Disease. MMWR 1987; 36: 1S-15S.
Scheper-Hughes N. AIDS, public health and human rights in Cuba. Lancet 1993; 342: 965–967.
Kaplan EL & Meier P. Nonparametric estimation from incomplete observations. J Amer Statist Ass 1958; 53: 457–481.
Friedman LM, Furberg CD & DeMets DL (eds). Fundamentals of Clinical Trials: Chapter 14. Survival Analysis, 2nd. edition, PSG Publishing Company, INC, Littleton, MA, 1985 pp 191–211.
Ezkowitz RAB, Mulliken JB & Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1992; 326: 1456–63.
Chang Y, Cesarman E & Pessin MS et al. Identification of new human herpesvirus-like KNA sequences in AIDS-associated Kaposi’s sarcoma. Science 1994; 266: 1865–69
Huang YQ, Li JJ & Kaplan MH et al. Human herpesvirus-like nucleic acid in various forms of Kaposi’s sarcoma. Lancet 1995; 345: 759–61
Morfeldt L & Torsander J. Long-term remission of Kaposi’s sarcoma following foscarnet treatment in HIV-infected patients. Scand J Infect Dis 1994; 26: 749–52
Costagliola D & Mary-Krause M. Can antiviral agents decrease the occurrence of Kaposi’s sarcoma? Lancet 1995; 346: 578
Kovacs JA, Baseler M & Dewar RJ et al. Increases in CD4 T lymphocytes with intermitent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N Engl J Med 1995; 332 (9): 567–75.
Simberkoff MS, Hartigan PM & Hamilton JD et al. Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 11(2): 142–50
Connor EM, Sperling RS & Gelber R et al. Reduction of maternal-infant tranmission of human immunodeficiency virus type I with zidovudine treatment. N Engl J Med 1994; 331: 1173–80
Zaretsky MD. AZT toxicity and AIDS prophylaxis: is AZT beneficial for HIV+ asymptomatic persons with 500 or more T4 cells per cubic millimeter? Genetica 1995; 95(1–3): 91–101
Volberding P. The value of the CD4+ count of 500 cells/microliters. Drugs 1995; 49 Suppl 1: 4–8
Kunzi MS, Farzadegan H, Margolick JB, Vlahov D & Pitha PM. Identification of human immunodeficiency virus primary isolates resistant to interferon-alpha and correlation of prevalence to disease progression. J Infect Dis 1995; 171(4): 822–8
Bissuel F, Trabaud MA & Leriche K et al. Tolerance of a triple combination therapy with zidovudine, didanosine and interferon-alpha in seven HIV-infected patients. AIDS 1995; 9(11): 1285
Garaci E, Rocchi G & Perroni L et al. Combination treatment with zidovudine, thymosin alpha-1 and interferon-alpha in human immunodeficiency virus infection. Int J Clin Lab Res 1994; 24(1): 23–8
Puppo F, Orlando G, Torresin A, Papa D, Balleari E, Criscuolo D & Indiveri F. Low doses of alpha interferon for the treatment of AIDS related syndromes: a preliminary study. Int J Immunotherapy 1988; 4: 165–8.
Lane HC, Davey V, Kovacs JA, Feinberg J, Metcalf JA & Herpin B et al. Interferon alpha in patients with asymptomatic Human Immunodeficiency Virus (HIV) infection. A randomized, placebo-controlled trial. Ann Int Med 1990; 112: 805–11.
Jordan WC. Three open-label studies of oral interferon alpha in the treatment of HIV disease. J Natl Med Assoc 1994; 86(4): 257–62.
Hulton MR, Levin DL & Freedman LS. Randomized, Placebo-Controlled, Double- Blind Study of Low-DoseOral Interferon-α in HIV-1 Antibody Positive Patients. J of Acquired Inmune Deficiency Syndromes 1992; 5: 1084–90.
Sperber SJ, Gocke DJ, Haberzettl CA & Petska S. Low-dose oral recombinant interferon-alpha-a in patients with HIV-1 infection. A blinded pilot study. AIDS 1993; 7(5): 693–7.
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Rivero, J., Fraga, M., Cancio, I. et al. Long-term treatment with recombinant interferon alpha-2b prolongs survival of asymptomatic HIV-infected individuals. Biotherapy 10, 107–113 (1997). https://doi.org/10.1007/BF02678537
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DOI: https://doi.org/10.1007/BF02678537