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Der Internist pp 103-111 | Cite as

Therapie und Immunprophylaxe der HIV-Infektion*

  • M. Vogt
  • R. Lüthy
  • W. Siegenthaler
Chapter

Zusammenfassung

Bei der Bekämpfung der AIDS-Epidemie wird eine wirksame Vakzine zur Prophylaxe einer Infektion mit dem Human Immunodeficiency Virus (HIV-1) dringend benötigt. Antivirale Substanzen sollen andererseits Krankheitssymptome und Tod bei bereits infizierten Personen verhindern. Besprochen werden anhand der einzelnen HIV-Replikationsschritte mögliche Angriffspunkte antiviraler Substanzen und die bisher verfügbaren Resultate experimenteller und klinischer Studien. Die heute vorliegenden Vakzine-Kandidaten werden kurz vorgestellt und zukünftige Entwicklungen und Probleme erörtert.

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Literatur

  1. 1.
    Anand R, Moore J, Feorino P, Curran J, Srinivasan A (1986) Rifabutine inhibits HTLV-III. Lancet 11:97–98CrossRefGoogle Scholar
  2. 2.
    Baba M, Pauwels R, Herdewijn P, De Clercq E, Desmyter J, Vandeputte M (1987) Both 2′,3′-dideoxythyrnidine and its 2′,3′-unsaturated derivative (2′,3′-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. Biochem Biophys Res Commun 142:128–134PubMedCrossRefGoogle Scholar
  3. 3.
    Balzarini J, Pauwels R, Herdewijn P, De Clercq E, Cooney DA, Kang G-J, Dalai M, Johns DG, Broder S (1986) Potent and selective anti-HTLV-III/LAV activity of 2′,3′-dideoxy-cytidinene, the 2′,3′-unsaturated derivative of 2′,3′-dideoxy-cytidine. Biochem Biophys Res Comm 140:735–742PubMedCrossRefGoogle Scholar
  4. 4.
    Barnes DM (1986) Strategies for an AIDS vaccine. Science 233:1149–1153PubMedCrossRefGoogle Scholar
  5. 5.
    Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamarei S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montaigner L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome. Science 220:868–871PubMedCrossRefGoogle Scholar
  6. 6.
    Buimovici-Klein E, Ong KR, Lange M, Englard A, McKinley GF, Reddy M, Grieco MH, Cooper LZ (1986) Reverse transcriptase activity (RTA) in lymphocyte cultures of AIDS patients treated with HPA-23. AIDS Res Ther 2:279–283Google Scholar
  7. 7.
    Carter WA, Strayer DR, Brodsky I, Lewin M, Pellegrino MG, Einck L, Henriques HF, Simon GL, Parenti DM, Scheib RG, Schuloff RS, Montefiori DC, Robinson WE, Mitchell WM, Volsky DJ, Paul D, Paxton H, Meyer WA, Kariko K, Reichenbach N, Suhadolnik RJ, Gillespie DH (1987) Clinical, immunological, and virological effects of ampligen, a mismatched double stranded RNA, in patients with AIDS or AIDS related complex. Lancet 1:1286–1292PubMedCrossRefGoogle Scholar
  8. 8.
    Chaisson RE, Allain J-P, Volberding PA (1986) Significant changes in HIV antigen level in the serum of patients treated with azidothymidine. N Engl J Med 315:1610–1611PubMedCrossRefGoogle Scholar
  9. 9.
    Chakrabarti S, Robert-Guroff M, Wong-Staal F, Gallo RC, Moss B (1986) Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature 320:535–537PubMedCrossRefGoogle Scholar
  10. 10.
    Cheson BD, Levine A, Mildvan D, Kaplan L, Rios A, Wolfe P, Groopman J, Hawkins M J (1986) Suramin therapy in AIDS and related diseases. Initial report of the US suramin working group. Proceedings International Conference on AIDS, Paris, June 23–25Google Scholar
  11. 11.
    Clark SC, Kamen R (1987) The human hematopoietic colony-stimulating factors. Science 236:1229–1237PubMedCrossRefGoogle Scholar
  12. 12.
    Clavel F, Guyader M, Guetard D, Salle M, Montagnier L, Alizon M (1986) Molecular cloning and polymorphism of the human immune deficiency virus type 2. Nature 324:691–695PubMedCrossRefGoogle Scholar
  13. 13.
    Clavel F, Mansinho K, Chamaret S, Guetard D, Favier V, Nina J, Santos-Ferreira M-O, Champalimaud JL, Montagnier L (1987) Human Immunodeficiency virus type 2 infection associated with AIDS in West Africa. N Engl J Med 316:1180–1185PubMedCrossRefGoogle Scholar
  14. 14.
    Coffin J, Haase A, Levy JA, Montagnier L, Oroszlan S, Teich N, Ternin H, Toyoshima K, Varmus H, Vogt P, Weiss R (1986) Human immunodeficiency viruses. Science 232:697PubMedCrossRefGoogle Scholar
  15. 15.
    Dahlberg JE, Mitsuya H, Blam SB, Broder S, Aaronson SA (1987) Broad spectrum antiretroviral activity of 2′,3′-di-deoxynucleosides. Proc Natl Acad Sci USA 84:2469–2473PubMedCrossRefGoogle Scholar
  16. 16.
    Dalgleish AG, Beverley PCL, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1984) The CD4 (T4) antigen is an essential component of the receptor of the AIDS retrovirus. Nature 312:763–767PubMedCrossRefGoogle Scholar
  17. 17.
    De Clercq E (1979) Suramin: A potent inhibitor of the reverse transcriptase of RNA tumor viruses. Cancer Lett 8:9–22PubMedCrossRefGoogle Scholar
  18. 18.
    Dormont D, Spire B, Barre-Sinoussi F, Montagnier L, Chermann JC (1985) Inhibition of RNA-dependent DNA polymerases of AIDS and SAIDS retroviruses by HPA-23 (Ammonium-21-tungsto-9-antimoniate). Ann Inst Pasteur Virol 136E: 75–83CrossRefGoogle Scholar
  19. 19.
    Ezzell C (1987) Trials of vaccine to begin in humans (News Editorial). Nature 328:747PubMedGoogle Scholar
  20. 20.
    Farber V, Dalgleish AG, Newell A, Malkowsky M (1987) Inhibition of HIV replication in vitro by fusidic acid. Lancet 11:827–828CrossRefGoogle Scholar
  21. 21.
    Farthing CF, Dalgleish AG, Clark AL, Chanas A, McClure M, Gazzard BG (1986) Pilot study on the treatment of AIDS and ARC patients with intravenous foscarnet. Proceedings International Conference on AIDS, Paris, June 23–25Google Scholar
  22. 22.
    Fauci AS, Rosenberg SA, Sherwin SA, Dinarello CA, Longo DL, Lane C (1987) Immunomodulators in clinical medicine. Ann Int Med 106:421–433PubMedCrossRefGoogle Scholar
  23. 23.
    Fischel MA, Richman DD, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, Leedom JM, Groopman JE, Mildvan D, Schooley RT, Jackson GG, Durack DT, King DK, and the AZT collaborative working group (1987) 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 317:185–191CrossRefGoogle Scholar
  24. 24.
    Francis DF, Petricciani JC (1985) The prospects for and pathways toward a vaccine for AIDS. N Engl J Med 313:1586–1590PubMedCrossRefGoogle Scholar
  25. 25.
    Furman PA, Fyfe JA, St. ClairMH, Weinhold K, Rideout JL, Freeman GA, Nusinoff Lehrman S, Bolognesi DP, Broder S, Mitsuya H, Barry DW (1986) Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci USA 83:8333–8337PubMedCrossRefGoogle Scholar
  26. 26.
    Gallo RC, Salahuddin S, Popovic M, Shearer GM, Kaplan M, Haynes BF, Palker TJ, Redfield R, Oleske J, Safai B, White G, Foster P, Markham PD (1984) Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science 224:500–503PubMedCrossRefGoogle Scholar
  27. 27.
    Gilbert BE, Knight V (1986) Biochemistry and clinical applications of ribavirin. Antimicrob Agents Chemother 30:201–205PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Groopman JE, Mitsuyasu RT, DeLeo MJ, Oette DH, Golde DW (1987) Effect of recombinant granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 317:593–598PubMedCrossRefGoogle Scholar
  29. 29.
    Hall CB, McBride JT, Walsh EE, Bell DM, Gala CL, Hil-dreth S, Ten Eyck LG, Hall WJ (1983) Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. N Engl J Med 308:1443–1447PubMedCrossRefGoogle Scholar
  30. 30.
    Hartmann H, Hunsmann G, Eckstein F (1987) Inhibition of HIV-induced cytopathogenicity in vitro by 3′-azido-2′,3′-dideoxyguanosine. Lancet II: 40–41CrossRefGoogle Scholar
  31. 31.
    Hartshorn K, Hirsch MS (1987) Interferons. In: Peterson PK, Verhoef J (eds) Antimicrobial Agents Annual 2. Elsevier, AmsterdamGoogle Scholar
  32. 32.
    Hartshorn KL, Neumeyer D, Vogt MW, Schooley RT, Hirsch MS (1987) Activity of interferons alpha, beta, gamma against human immunodeficiency virus replication in vitro. AIDS Res Hum Retrovir 3:125–133PubMedCrossRefGoogle Scholar
  33. 33.
    Hartshorn KL, Vogt MW, Chou T-C, Blumberg RS, By-ington R, Schooley RT, Hirsch MS (1987) Synergistic inhibition of human immunodeficiency virus in vitro by azi-dothymidine and recombinant alpha A interferon. Antimic-rob Agents Chemother 31:168–172CrossRefGoogle Scholar
  34. 34.
    Ho DD, Hartshorn KL, Rota TR, Andrews CA, Kaplan JC, Schooley RT, Hirsch MS (1985) Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro. Lancet 11:602–604CrossRefGoogle Scholar
  35. 35.
    Ho DD, Rota TR, Hirsch MS (1986) Infection of monocyte/ macrophages by human T-lymphotropic virus type III. J Clin Invest 77:1712–1715PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Ho DD, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, Resnick L, Felsenstein D, Andrews CA, Hirsch MS (1985) Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 313:1493–1497PubMedCrossRefGoogle Scholar
  37. 37.
    Hu S-L, Fultz PN, McClure HM, Eichberg JW, Thomas EK, Zarling J, Singhai MC, Kosowski SG, Swenson RB, Anderson DC, Todaro G (1987) Effect of immunization with a vaccinia-HIV env recombinant on HIV infection of chimpanzees. Nature 328:721–723PubMedCrossRefGoogle Scholar
  38. 38.
    Hu SL, Kosowski SG, Galrymple JM (1986) Expression of AIDS virus envelope genein recombinant vaccinia viruses. Nature 320:537–540PubMedCrossRefGoogle Scholar
  39. 39.
    Kimberlin RH, Walker AC (1986) Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. Antimicrob Agents Chemother 30:409–413PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Klecker RW, Collins JM, Yarchoan M, Thomas R, Jenkins JF, Broder S, Myers CE (1987) Plasma and cerebrospinal fluid pharmacokinetics of 3’-azido-3’-deoxythymidine: A novel pyrimidine analog with potential applications for the treatment of patients with AIDS and related diseases. Clin Pharmacol Ther 41:407–412PubMedCrossRefGoogle Scholar
  41. 41.
    Krohn K, Robey WG, Putney S, Arthur L, Nara P, Fisch-inger P, Gallo RC, Wong-Staal F, Ranki A (1987) Specific cellular immune response and neutralizing antibodies in goats immunized with native or recombinant envelope proteins derived from human T-lymphotropic virus type HIB and in human immunodeficiency virus-infected men. Proc Natl Acad Sci USA 84:4994–4998PubMedCrossRefGoogle Scholar
  42. 42.
    Levy JA, Hoffman AD, Landis JA, Shimabukuro JM, Oshiro LS (1984) Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 225:840–842PubMedCrossRefGoogle Scholar
  43. 43.
    Levy JA, Shimabukuro J, Hollander H, Mills J, Kaminsky L (1985) Isolation of AIDS associated retroviruses from cerebro-spinal fluid and brain of patients with neurological symptoms. Lancet II: 586–588Google Scholar
  44. 44.
    McCormick JB, King I, Webb PA, Scribner CL, Craven RB, Johnson KM, Elliott LH, Belmont-Williams R (1986) Lassa fever. Effective therapy with ribavirin. N Engl J Med 314:20–26PubMedCrossRefGoogle Scholar
  45. 45.
    Mitsuya H, Broder S (1986) Inhibition of the in vitro infec-tivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/ LAV) by 2′,3′-dideoxynucleosides. Proc Natl Acad Sci USA 83:1911–1915PubMedCrossRefGoogle Scholar
  46. 46.
    Mitsuya H, Broder S (1987) Strategies for antiviral therapy in AIDS. Nature 325:773–778PubMedCrossRefGoogle Scholar
  47. 47.
    Mitsuya H, Jarrett RF, Matsukura M, Di Marzo-Veronese F, DeVico AL, Sarngadharan MG, Johns DG, Reitz MS, Broder S (1987) Long-term inhibition of human T-lymphotropic virus type-III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T-cells protected by 2′,3′-dideoxynucleosides in vitro. Proc Natl Acad Sci USA 84:2033–2037PubMedCrossRefGoogle Scholar
  48. 48.
    Mitsuya H, Popovic M, Yarchoan R, Matsushita S, Gallo RC, Broder S (1984) Suramin protection of T-cells in vitro against infectivity and cytopathic effect of HTLV-IIII. Science 226:172–174PubMedCrossRefGoogle Scholar
  49. 49.
    Mitsuya H, Weinhold KJ, Furman PA, Clair MH, Nusinoff-Lehrman S, Gallo RC, Bolognesi D, Barry DW, Broder S (1985) 3′-Azido-3′-deoxythymidine (BW A509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/ lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci USA 82:7096–7100PubMedCrossRefGoogle Scholar
  50. 50.
    Nicholson JKA, Cross GD, Callaway CS, McDougal JS (1986) In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol 137:323–329PubMedGoogle Scholar
  51. 51.
    Oberg B (1983) Antiviral effects of phosphonoformate (PFA, Foscarnet sodium). Pharm Ther 19:387–415CrossRefGoogle Scholar
  52. 52.
    Osterhaus A, Weijer K, Uytdehaag F, Jarrett O, Sundquist B, Morein B (1985) Induction of protective immune response in cats by vaccination with feline leukemia virus ISCOM. J Immunol 135:591–596PubMedGoogle Scholar
  53. 53.
    Pert CB, Hill JM, Ruff MR, Berman RM, Robey WG, Arthur LO, Ruscetti FW, Farrar WL (1986) Octapeptides deduced from the neuropeptide receptor like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity. Proc Natl Acad Sci USA 83:9254–9258PubMedCrossRefGoogle Scholar
  54. 54.
    Richman DD, Fischel MA, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, Leedom JM, Groopman JE, Mildvan D, Hirsch MS, Jackson GG, Durack DT, Nusinoff-Lehrman S, and the AZT Collaborative Working Group (1987) The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 317:192–197PubMedCrossRefGoogle Scholar
  55. 55.
    Rosen CA, Sodroski JG, Goh WC, Dayton AI, Lippke J, Haseltine WA (1986) Post-transcriptional regulation accounts for the transactivation of the human T-lymphotropic virus type III. Nature 319:555–559PubMedCrossRefGoogle Scholar
  56. 56.
    Sandstrom EG, Kaplan JC, Byington RE, Hirsch MS (1985) Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate. Lancet 1:1480–1482PubMedCrossRefGoogle Scholar
  57. 57.
    Sarin PS, Gallo RC, Scheer DI, Crews F, Lippa AS (1985) Effect of a novel compound (AL 721) on HTLV-III infectivity in vitro. N Engl J Med 313:1289–1290PubMedCrossRefGoogle Scholar
  58. 58.
    Sarin PS, Sun D, Thornthon A, Muller WG (1987) Inhibition of replication of the etiologic agent of acquired immune deficiency syndrome (Human T-lymphotropic retrovirus/ lymphadenopathy-associated virus) by Avarol and Avar-one. JNCI 78:663–666PubMedGoogle Scholar
  59. 59.
    Scheib RS, Parenti DM, Simon GL, Digioia RA, Sarin PS, Chandra P, Schulof RS (1986) D-Penicillamine (DPA) for the treatment of HTLV-III/LAV infection. Program and abstracts of the 26th Interscience Conference on antimicrobial agents and chemotherapy, New OrleansGoogle Scholar
  60. 60.
    Sodroski J, Goh WC, Rosen C, Dayton A, Terwilliger E, Haseltine W (1986) A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature 321:412–417PubMedCrossRefGoogle Scholar
  61. 61.
    Sodroski J, Kowalski M, Dorfman T, Basiripour L, Rosen C, Haseltine W (1987) HIV Envelope-CD4 interaction not inhibited by synthetic octapeptides. Lancet 1:1428–1429PubMedCrossRefGoogle Scholar
  62. 62.
    Sommadossi J-P, Carlisle R (1987) Toxicity of 3′-azido-3′-deoxythymidine and 9-(l,3-dihydroxy-2-propoxymethyl)-guanine for normal human hematopoietic progenitor cells in vitro. Antimicrob Agents Chemother 31:452–454PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Stein BS, Gowda SD, Lifson JD, Penhallow RC, Bensch KG, Engleman EG (1987) ph-independent HIV entry into CD4-positive T-cells via virus envelope fusion to the plasma membrane. Cell 49:659–668PubMedCrossRefGoogle Scholar
  64. 64.
    Ueno R, Kuno S (1987) Dextran sulfate, a potent anti-HIV agent in vitro having synergism with zidovudine. Lancet 1:1379PubMedCrossRefGoogle Scholar
  65. 65.
    Vogt M, Coleman LA, Hirsch MS (1987) Therapeutische Möglichkeiten bei Infektionen mit dem AIDS-Virus HIV (human immunodeficiency virus). In: Siegenthaler W (ed) Aktuelle Aspekte der Infektiologie; 19. Symposium der Gesellschaft für Fortschritte auf dem Gebiet der Inneren Medizin. Thieme, StuttgartGoogle Scholar
  66. 66.
    Vogt M, Hirsch MS (1986) Prospects for the prevention and therapy of HTLV-III infections. Rev Infect Dis 8:991–1000PubMedCrossRefGoogle Scholar
  67. 67.
    Vogt MW, Hartshorn KL, Furman PA, Chou T-C, Fyfe JA, Coleman LA, Crumpacker C, Schooley RT, Hirsch MS (1987) Ribavirin antagonizes the effect of azidothymidine on HIV replication. Science 235:1376–1379PubMedCrossRefGoogle Scholar
  68. 68.
    Vogt MW, Hirsch MS (1987) Treatment of human immunodeficiency virus infections. In: V Knight, BE Gilbert (eds) Antiviral Chemotherapy. Infect Dis Clin North Am. Saunders, Philadelphia, pp 323–339Google Scholar
  69. 69.
    Walker BD, Chakrabarti S, Moss B, Paradis TJ, Flynn T, Durno AG, Blumberg RS, Kaplan JC, Hirsch MS, Schooley RT (1987) HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 328:345–348PubMedCrossRefGoogle Scholar
  70. 70.
    Weiss R, Teich N, Varmus H, Coffin J (eds) (1985) RNA tumor viruses — molecular biology of tumor viruses, 2. ed, Vol 2. Cold Spring Harbor Laboratory, New YorkGoogle Scholar
  71. 71.
    Wong-Staal F, Gallo RC (1985) Human T-lymphotropic retroviruses. Nature 317:395–403PubMedCrossRefGoogle Scholar
  72. 72.
    Yarchoan R, Berg G, Browers P, Fischel MA, Spitzer AR, Wichman A, Grafman J, Thomas RV, Safai B, Brunetti A, Perno CF, Schmidt PJ, Larson SM, Myers CE, Broder S (1987) Response of human-immunodefîciency virus associated neurological disease to 3′-azido-3′-deoxythymidine. Lancet 1:132–135PubMedCrossRefGoogle Scholar
  73. 73.
    Yarchoan R, Klecker RW, Weinhold KJ, Markham PD, Lyerly HK, Durack DT, Gelmann E, Nusinoff Lehrmann S, Blum RM, Barry DW, Shearer GM, Fischl MA, Mitsuya H, Gallo RC, Collins JM, Bolognesi DP, Myers CE, Broder S (1986) Administration of 3′-azido-3′-deoxythymidine, an inhibitor of HTLV-III replication, to patients with AIDS and AIDS-Related-Complex. Lancet 1:575–580PubMedCrossRefGoogle Scholar
  74. 74.
    Zamecnik PC, Goodchild J, Taguchi Y, Sarin PS (1986) Inhibition of replication and expression of human T-cell lymphotropic virus type III in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA. Proc Natl Acad Sci USA 83:4143–4146PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • M. Vogt
    • 1
    • 2
  • R. Lüthy
    • 1
  • W. Siegenthaler
    • 1
  1. 1.Abteilung für Infektionskrankheiten, Departement für Innere MedizinUniversitätsspital ZürichDeutschland
  2. 2.Abteilung für Infektionskrankheiten Departement für Innere MedizinMedizinische Poliklinik UniversitätsspitalZürichSchweiz

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