Biotherapy

, Volume 8, Issue 1, pp 23–31 | Cite as

Use of recombinant interferon-α in Human Immunodeficiency Virus (HIV)-infected individuals

  • J. Rivero
  • M. Limonta
  • A. Aguilera
  • M. Fraga
  • P. López Saura
Article

Rationale and objective

Interferon alpha (IFN-α) has anti-retroviral activity and is a possible HIV infection-limiting factor. The aim of this work is to prevent or delay disease progression in asymptomatic Human Immunodeficiency Virus (HIV) carriers.

Design and interventions

Recombinant IFN alpha-2b (3×106 IU 3 times weekly) was compared. to no treatment (control) in a randomized trial. Endpoints were: (i) appearance of any CDC group IV symptoms and (ii) disease progression (which excluded shifts to group IVC2 or reversible IVA, or IVB). The trial lasted from October 1987 to February 1992.

Setting

The trial was performed at the “Santiago de las Vegas” sanatorium, a specialized institution for the care of HIV-infected and AIDS patients.

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 71 (IFN) patients.

Main results

Long-term IFN-α treatments significantly reduced the proportion of patients who shifted to any group IV (control: 46/79; IFN: 14/71;p<0.001) or developed AIDS (control: 27/79; IFN: 12/71;p<0.05). IFN also delayed progression to AIDS (95% confidence interval for 0.5 probability of progression) from 67–83 to 116–180 months after infection. The IFN group had significantly less opportunistic infections and non-infectious complications. CD4 cell count and hemoglobin decreased in the control but not in the IFN group. Fewer IFN-treated patients developed positive serum HIV antigen detection.

Conclusion

IFN alpha treatment during the early stages of infection seems to be beneficial to the patients.

Key words

Interferon alpha AIDS HIV infection HIV carriers 

Abbreviations

CI

confidence interval

AIDS

Acquired Immunodeficiency syndrome

HIV

Human Immunodeficiency Virus

IFN

Interferon

CDC

Center for Disease Control (USA)

SD

standard deviation

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References

  1. 1.
    Mann J, Tarantola DJM, and Netter TW, eds. AIDS in the world 1992, Chapter 1. Cambridge: Harvard University Press, 1992: 1–14.Google Scholar
  2. 2.
    Pitha PM, Wivel NA, Fernie VF, and Harper HP. Effect of Interferon on murine leukemia virus infection. IV. Formation of non-infectious virus in chronically infected cells. J Gen Virol 1979, 42: 467–80.PubMedGoogle Scholar
  3. 3.
    Poli G, Orenstein JM, Kinter A, Folks TM, and Fauci AS, Interferon alpha but not AZT suppresses HIV expression in chronic;ally infected cell lines. Science 1989: 244: 575–77.PubMedGoogle Scholar
  4. 4.
    Ho DD, Hartshorn KL, Rota TR, Andrews CA, Kaplan GC, Schooley RT, and Hirsch MS, Recombinant human interferon alpha-A suppresses HTLV-III replication in vitro. Lancet 1985: i: 602–4.Google Scholar
  5. 5.
    Yamamoto JK, Barre-Sinoussi F, Bolton V, Pedersen NC, and Gardner MB, Human alpha and beta interferons but not gamma suppress the in vitro replication of LAV, HTLV III and ARV-2. J Interferon Res 1986: 6: 143–52.PubMedGoogle Scholar
  6. 6.
    Hartshorn KL, Neumeyer D, Vogt MW, Schooley RT, and Hirsch MS, Activity of interferon alpha, beta and gamma against Human Immunodeficiency Virus replication in vitro. AIDS Res Human Retroviruses 1987: 3: 125–32.Google Scholar
  7. 7.
    Smith MS, Thresher RJ, and Pagano JS, Inhibition of Human Immunodeficiency Virus type 1 morphogenesis in T-cells by alpha IFN. Antimicrob Chemother 1991: 35: 62–8.Google Scholar
  8. 8.
    Gendehnan HE, Baca LM, Turpin J, Kalter DC, Hansen B, Orenstein JM, et al., Regulation of HIV replication in infected monocytes by IFN alpha: mechanism for viral restriction. J Immunol 1990: 145: 2669–73.PubMedGoogle Scholar
  9. 9.
    Dubreuil M, Sportza L, D'Addario M, Lacoste J, Rooke R, Wainberg MA, et al., Inhibition of HIV-1 transmission by Interferon and 3′-azido-3′-deoxythymidine during de novo infection of promonocytic cells. Virology 1990: 179: 388–94.PubMedGoogle Scholar
  10. 10.
    Gendelman HE, Baca L, Turpin JA, Kalter DC, Hansen BD, Orenstein JM, et al., Restriction of HIV replication in infected T-cells and monocytes by interferon alpha. AIDS Res Human Retroviruses 1990: 6: 1045–49.Google Scholar
  11. 11.
    Kornbluth RS, Oh PS, Munis JR, Cleveland PH, and Richman DD, Interferons and bacterial lipopolysaccaharide protect macrophages from productive infection by HIV in vitro. J Exp Med 1989: 169: 1137–42.PubMedGoogle Scholar
  12. 12.
    Krown SE, Real FX, Cunningham-Rundles S, Myskowski PL, Koziner B, Fein S, et al., Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi's Sarcoma. N Engl J Med. 1983: 308: 1071–76.PubMedGoogle Scholar
  13. 13.
    DeWit R, Schattenkerk JKME, Boucher CAB, Bakker PJM, Veenhof KHN, and Danner SA, Clinical and virological effects of high doses recombinant interferon alpha in disseminated AIDS-related Kaposi's Sarcoma. Lancet 1988: 2: 1214–17.PubMedGoogle Scholar
  14. 14.
    Lane HC, Kovacs JA, Feinberg J, Herpin B, Davey V, Walker R, et al., Antiretroviral effects of interferon alpha in AIDS-associated Kaposi's Sarcoma. Lancet 1988: 2: 1218–22.PubMedGoogle Scholar
  15. 15.
    López C, Fitzgerald PA, and Segal FP, Severe Acquired Immunodeficiency Syndrome in male homosexuals: diminished capacity to make interferon alpha in vitro associated with severe opportunistic infections. J Infect Dis 1983: 148: 962–66.PubMedGoogle Scholar
  16. 16.
    Voth R, Rossol S, Klein K, Hess G, Schutt KH, Schroder HC, et al., Differential gene expression of interferon alpha and tumor necrosis factor alpha in peripheral blood mononuclear cells from patients with AIDS-related complex and AIDS. J Immunol 1990: 144: 970–75.PubMedGoogle Scholar
  17. 17.
    Lau AS, Read SE, Williams BRG, Down-regulation of interferon alpha but not gamma receptor expression in vivo in the Adquired Immunodeficiency Syndrome. J Clin Invest 1988: 82: 1415–21.PubMedGoogle Scholar
  18. 18.
    DeStefano S, Friedman RM, Friedman-Kien AE, Goedert JJ, Henriksen D, Preble OT, et al., Acid-labile human leukocyte interferon in homosexual men with Kaposi's Sarcoma and lymphadenopathy. J Infect Dis 1982: 146: 451–55.PubMedGoogle Scholar
  19. 19.
    Abb J, Zachoval R, Zachoval V, and Deinhardt F, HIV antigen, HIV antibody and serum interferon in a patient with encephalopathy. Infection 1987: 15: 425–26.PubMedGoogle Scholar
  20. 20.
    Szab _B, T_th D, Kiss J, Ujhelyi E, F_st G, Horv_th A, and Holl_n SR, Neutralizing antibodies and serum interferon levels in the different stages of HIV infection. Acta Virol 1990: 34: 164–70.PubMedGoogle Scholar
  21. 21.
    Vonsydow M, Sonnerborg A, Gaines H, and Strannergard O, Interferon alpha and Tumor Necrosis Factor alpha in Serum of patients in Various Stages of HIV-1 infection. AIDS Res Human Retroviruses 1991: 7: 375–80.Google Scholar
  22. 22.
    Preble OT, Rook AH, Quinnan QV, Vilcek J, Friedman RM, Steis R, et al. Role of Interferon in AIDS. Ann NY Acad Sci 1985: 437: 65–75.Google Scholar
  23. 23.
    Francis ML, Meltzer MS, and Gendelman HE, Interferons in the persistence, pathogenesis and treatment of HIV infection. AIDS Res Human Retroviruses 1992: 8: 199–207.Google Scholar
  24. 24.
    Puppo F, Orlando G, Torresin A, Papa D, Balleari E, Criscuolo D, and Indiveri F, Low doses of alpha interferon for the treatment of AIDS related syndromes: a preliminary study. Int J Immunotherapy 1988; 4: 165–8Google Scholar
  25. 25.
    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.PubMedGoogle Scholar
  26. 26.
    Hulton MR, Levin DL, Freedman LS. Randomized, Placebo-Controlled, Double-Blind Study of Low-Dose Oral Interferonα in H1V-1 Antibody Positive Patients. J of Acquired Immune Deficiency Syndromes 5: 1084–90., 1992.Google Scholar
  27. 27.
    Sperber SJ, Gocke DJ, Haberzettl CA, and Petska S, Lowdose oral recombinant interferon-alpha-a in patients with HIV-1 infection. A blinded pilot study. AIDS, 1993; 7(5): 693–97.PubMedGoogle Scholar
  28. 28.
    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.Google Scholar
  29. 29.
    Rivero J, Gonz_lez A, Ram_rez; V, López-Saura P, and Limonta M, Use of Alfa-Interferon in HIV-infected patients in Cuba. J Interferon Res 1988: 8: S87.Google Scholar
  30. 30.
    Rivero J, Limonta M, Ram_rez V, Gonz_lez A, Aguilera and López-Saura P. Long-Term Treatment with Recombinant or Natural Alfa Interferon in Asymptomatic Seropositive HIV-Carriers Prolongs the Incubation Period (Abst). J Interferon Res 1990: 10: S16.Google Scholar
  31. 31.
    Rivero J, Limonta M, Ram_rez V, Gonz_lez A, Aguilera A, and López-Saura P, Alfa Interferon is useful in seropositive asymptomatic HIV-infected individuals (Abst). J Interferon Res 1991: 11: S77.Google Scholar
  32. 32.
    Kaplan EL, Meier P, Nonparametric estimation from incomplete observations. J Amer Statist Ass 1958: 53: 457–81.Google Scholar
  33. 33.
    Friedman, LM, Furberg, CD, and DeMets, DL (eds), Fundamentals of Clinical Trials: Chapter 14. Survival Analysis, 2nd. edition, PSG Publishing Company, INC, Littleton, MA, 1985 pp 191–211Google Scholar
  34. 34.
    Cai Q, Huang XL, Rappocciolo Cr, and Rinaldo CR, Natural Killer Cell responses in homosexual men with early HIV infection. J Acq Immun Defic Syndrome 1990: 3: 669–76.Google Scholar
  35. 35.
    Ho DD, Moudgil T, and Alam M, Quantitation of Human Immunodeficiency Virus Type I in the blood of infected persons. N Engl J Med 1989: 321: 1621–25.PubMedGoogle Scholar
  36. 36.
    Scheper-Hughes, N, AIDS, public; health and human rights in Cuba. Lancet 1993: 342: 965–67.PubMedGoogle Scholar
  37. 37.
    Gill PS, Rarick M, Byrnes RK, Causey D, Loureiro C, and Levine AM, Azidothymidine associated with bone marrow failure in the Adquired Immunodeficiency Syndrome (AIDS). Ann Int Med 1987: 107: 502–10.PubMedGoogle Scholar
  38. 38.
    Richman DD, Fischl MA, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, et al., The toxicity of Azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 1987: 317: 192–97.PubMedGoogle Scholar
  39. 39.
    Dournon E, The Claude Bernard Hospital AZT Study Group, Effects of Zidovudine in 365 consecutive patients with AIDS or AIDS-related complex. Lancet 1988: ii: 1297.Google Scholar
  40. 40.
    Baum MK, Javier JJ, Mantero-Atienza E, Beach RS, Fletcher MA, Sauberlich HE, et al., Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males. J Acq Immun Defic Syndrome 1991: 4: 1218–26.Google Scholar
  41. 41.
    Kovacs JA, Deyton L, Davey R, et al. Combined zidovudine and interferon-α therapy in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989; 111: 280–87.PubMedGoogle Scholar
  42. 42.
    Krown SE, Gold JWM, Niedzwiecki D, et al. Interferonα with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi's sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1990; 112: 812–21.PubMedGoogle Scholar
  43. 43.
    Fischl Ma, Uttamchandani RB, Resnick L, et al. A phase I study of recombiant human interferonα-2a or human lymphoblastoid interferonα-nl and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma: J Acquir Immune Defic Syndr 1991; 4: 1–10.PubMedGoogle Scholar
  44. 44.
    Deboer JB, Vandam FSAM, Sprangers MAG, Frissen PHJ, and Lange JM, Longitudinal study on the quality of life of symptomatic HIV-infected patients in a trial of zidovudine versus zidovudine and interferon-alpha. AIDS, 1993; 7 (7): 947–53PubMedGoogle Scholar
  45. 45.
    Fischl MA, Richman DD, Hansen N, et al., The safety and efficacy of Zidovudine (ZDV) in the treatment of subjects with mildly symptomatic Human Immunodeficiency Virus type 1 (HIV) infection. Ann Int Med 1990: 112: 727–37.PubMedGoogle Scholar
  46. 46.
    Hamilton JD, Hartigan PM, Simbrkoff MS, et al. A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection — results of the Veteran Affairs Cooperative Study. N Engl J Med 1992, 326: 437–43.PubMedGoogle Scholar
  47. 47.
    Neil MH, Graham NIB, Zeger SL, Park LP, Vermund SH, Deterls R, et al., The effects on survival of early treatment of Human Immunodeficiency Virus infection. N Engl J Med 1992, 326: 1037–42.PubMedGoogle Scholar
  48. 48.
    Aboulker JP and Swart AM, Preliminary analysis of the Concorde trial. Lancet 1993: 341: 889–90PubMedGoogle Scholar
  49. 49.
    Francis ML, Meltzer MS, and Gendelman HE, Interferons in the persistence, pathogenesis, and treatment of HIV infection. AIDS Res Human Retroviruses 1992: 8: 199–207.Google Scholar
  50. 50.
    Dolei A, Fattorossi A, D'Amelio R, Aiuti F, and Dianzani F, Direct and cell-mediated effects of interferons alpha and gamma on cells chronically infected with HTLV-III. J Interferon Res 1986: 6: 543–49.PubMedGoogle Scholar
  51. 51.
    Witt PL, Spear GT, Lindstrom MJ, Kessler HA, Borden EC, Phair J, and Landay AL, 2′5′-oligoadenylate synthetase, neopterin, andβ-2 microglobulin in asymptomatic HIV-infected individuals. AIDS 1991: 5: 289–93.PubMedGoogle Scholar
  52. 52.
    Gendelman HE, Friedman RM, Joe S, Baca LM, Turpin JA, Dveksler G, et al. A selective defect of inteferon alpha production in Human Immunodeficiency Virus infected monocytes. J Exptl Med 1990: 171: 1433–42.Google Scholar
  53. 53.
    Capobianchi MR, De Marco F, Di Marco P, and Dianzani F, Acid labile human interferon alpha production by peripheral blood mononuclear cells stimulated by HIV-infected cells. Arch Virol 1988: 99: 9–14.PubMedGoogle Scholar
  54. 54.
    Gendelman HE, Baca LM, Kubrak CA, Genis P, Burrous S, Friedman RM, et al., Induction of interferon alpha in peripheral blood mononuclear cells by HIV-infected monocytes. Restricted antiviral activity of HIV induced interferon. J Immunol 1992: 148: 422–29.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • J. Rivero
    • 1
  • M. Limonta
    • 2
  • A. Aguilera
    • 2
  • M. Fraga
    • 1
  • P. López Saura
    • 3
  1. 1.Santiago de las Vegas SanatoriumHavanaCuba
  2. 2.The Center for Genetic Engineering and BiotechnologyHavanaCuba
  3. 3.Center for Biological ResearchHavanaCuba

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