Dtsch Med Wochenschr 2001; 126(37): 1017-1022
DOI: 10.1055/s-2001-17113
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© Georg Thieme Verlag Stuttgart · New York

Immunrekonstitutionssyndrom

Ein neues Krankheitsbild bei HIV-Infizierten unter wirksamer antiretroviraler TherapieImmune reconstitution syndrome, a new disease in HIV-infected patients being successfully treated with antiretroviral drugsM. Stoll, G. M. N. Behrens, R. E. Schmidt
  • Abteilung Klinische Immunologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover
Further Information

Publication History

Publication Date:
28 April 2004 (online)

Der natürliche Verlauf der HIV-Infektion ist charakterisiert durch eine fortschreitende Destruktion des zellulären Immunsystems, der durch Surrogatmarker (CD4+ T-Lymphozytenzahl im peripheren Blut) abgeschätzt werden kann. Hochaktive antiretrovirale Kombinationstherapien (HAART) bewirken einen raschen Abfall der HI-Plasmavirämie und in der Folge eine Rekonstitution des Immunsystems, meßbar auch in einem signifikanten Anstieg der CD4+ T-Zellen im Blut.

Die unter HAART auftretende Immunrekonstitution hat wesentlichen Einfluß auf die Inzidenz opportunistischer Erkrankungen, aber auch auf den Verlauf prävalenter opportunistischer Infektionen und Autoimmunopathien.

Mit inflammatorischen Reaktionen einhergehende atypische Krankheitsbilder im Rahmen einer HAART bei HIV-Infizierten werden unter dem Begriff des »Immunrekonstitutionssyndroms« zusammengefaßt. Die Kenntnis dieser Krankheitsbilder ist von praktischer Bedeutung für den Kliniker. Diese Übersicht charakterisiert anhand des bisherigen publizierten Wissenstandes und an einer Reihe von eigenen Fällen die Vielfältigkeit und Besonderheiten von inflammatorischen Immunrekonstitutionssyndromen und gibt einen Überblick über den Stellenwert möglicher diagnostischer und therapeutischer Strategien.

The natural history of HIV infection is characterized by progressive destruction of the cellular immune system, which is reflected by decrease of CD4+ T-lymphocytes in peripheral blood. Inhibition of replicative HIV infection by use of highly active antiretroviral therapy (HAART) leads to reconstitution of the impaired immune system. In Western countries morbidity and mortality caused by HIV-infection could be decreased remarkably by whitespread use of HAART.

By improving the potency of the immune system HAART increases inflammatory responses and is able to change the individual course of prevalent subclinical opportunistic infections or autoimmune diseases.

Such atypical inflammatory disorders, which predominantly developed a short time after initiating HAART have been summarized as »immune reconstitution disorders«. The awareness for these diseases is clinically important for physicians treating HIV infected persons.

This review describes the pattern of immunoreconstitution disorders by summarizing the literature and presenting typical cases and will give an overview about possible diagnostical pitfalls and therapeutical options.

Literatur

  • 1 Aldeen T, Hay P, Davidson F, Lau R. Herpes zoster infection in HIV-seropositive patients associated with highly active antiretroviral therapy.  AIDS. 1998;  12 1719-1720
  • 2 Behrens G, Knuth C, Schedel I, Mendila M, Schmidt R E. Highly active antiretroviral therapy.  Lancet. 1998;  351 1057-1058
  • 3 Behrens G, Stoll M, Schmidt R E. Lipodystrophy syndrome with protease inhibitors: what is it, what causes it and how can it be managed?.  Drug Saf. 2000;  23 57-76
  • 4 Behrens G M, Meyer D, Stoll M, Schmidt R E. Immune reconstitution syndromes in human immuno deficiency virus infection following effective antiretroviral therapy.  Immunobiology. 2000;  202 186-193
  • 5 Behrens G MN, Stoll M, Schmidt R E. Pulmonary hypersensitivity reaction induced by efavirenz.  Lancet. 2001;  357 1503-1504
  • 6 Cameron D W, Heath C, Danner S. et al . Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group.  Lancet. 1998;  351 543-549
  • 7 Deayton J, Wilson P. et al . Changes in the natural history of cytomegalovirus retinitis following the introduction of highly antiretroviral therapy.  AIDS. 2000;  14(9) 1163-1170
  • 8 del Giudice P. et al . Mycobacterial cutaneous manifestations: a new sign of immune restoration syndrome in patients with acquired immunodeficiency syndrome.  Arch Dermatol. 1999;  135 1129-1130
  • 9 Douek D C, Koup R A. Evidence for thymic function in the elderly.  Vaccine. 2000;  18 1638-1641
  • 10 Draenert R, Goebel F. Empfehlungen und Perspektiven der antiretroviralen Therapie.  Dtsch Med Wochenschr. 2001;  126 539-543
  • 11 Dworkin M S, Fratkin M D. Mycobacterium avium complex lymph node abscess after use of highly active antiretroviral therapy in a patient with AIDS.  Arch Intern Med. 1998;  158 1828
  • 12 Fauci A S, Pantaleo G, Stanley S, Weissman D. Immunopathogenic mechanisms of HIV infection.  Ann Intern Med. 1996;  124 654-663
  • 13 Foudraine N A. et al . Immunopathology as a result of highly active antiretroviral therapy in HIV-1-infected patients.  AIDS. 1999;  13 177-184
  • 14 Furrer H, Egger M. et al . Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combination antiretroviral therapy. Swiss HIV Cohort Study.  N Engl J Med. 1999;  340 1301-1306
  • 15 Garweg J G. Affektionen der vorderen Augenabschnitte bei HIV-Infektion nach Einführung der hochaktiven antiretroviralen Therapie (HAART).  Klin Monatsbl Augenheilkd. 2000;  216 61-67
  • 16 Gea-Banacloche J C, Lane C. Immune reconstitution in HIV infection.  AIDS. 1999;  13 S25-S38 (Suppl A))
  • 17 Gilquin J, Viard J P. et al . Delayed occurrence of Graves’ disease after immune restoration with HAART.  Lancet. 1998;  352 1907-1908
  • 18 Giudici B, Vaz B. et al . Highly active antiretroviral therapy and progressive multifocal leukoencephalopathy.  Clin Infect Dis. 2000;  30 95-99
  • 19 Grosse V, Schulte A, Weber K, Mendila M, Jacobs R, Schmidt R E, Heiken H. Progressive reduction of CMV-specific CD4+ T cells in HIV-1 infected individuals during antiretroviral therapy.  Immunobiology. 2000;  202 179-185
  • 20 Hadad D J, Lewi D S. et al . Resolution of Mycobacterium avium complex bacteremia following highly active antiretroviral therapy.  Clin Infect Dis. 1998;  26 758-759
  • 21 John M, Flexman J, French M A. Hepatitis C virus-associated hepatitis following treatment of HIV-infected patients with HIV protease inhibitors: an immune restoration disease?.  AIDS. 1998;  12 2289-2293
  • 22 John M, French M A. Exacerbation of the inflammatory response to Mycobacterium tuberculosis after antiretroviral therapy.  Med J Aust. 1998;  169 473-474
  • 23 Kaufmann G R, Zaunders J, Cooper D A. Immune reconstitution in HIV-1 infected subjects treated with potent antiretroviral therapy.  Sex Transm Infect. 1999;  75 218-224
  • 24 Kaufmann G R. et al . Rapid restoration of CD4 T cell subsets in subjects receiving antiretroviral therapy during primary HIV-1 infection.  AIDS. 2000;  14 2643-2651
  • 25 Keruly J C, Chaisson R E, Moore R D. Increasing incidence of avascular necrosis of the hip in HIV-infected patients. Chicago Abstrakt 637 8th Conf Retrovir Opportun Infect 2001
  • 26 Laes A J, MacLeod A F, Marshall J. Cerebral tuberculomas developing during treatment of tuberculous meningitis.  Lancet. 1980;  I 1208-1211
  • 27 Martinez E. et al . High incidence of herpes zoster in patients with AIDS soon after therapy with protease inhibitors.  Clin Infect Dis. 1998;  27 1510-3
  • 28 Mayo J. et al . Progressive multifocal leukoencephalopathy following initiation of highly active antiretroviral therapy.  AIDS. 1998;  12 1720-1722
  • 29 Meyer D, Behrens G, Schmidt R E, Stoll M. Osteonecrosis of the femoral head in patients receiving HIV protease inhibitors.  AIDS. 1999;  13 1147-1148
  • 30 Miralles P. et al . Treatment of AIDS-associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy.  AIDS. 1998;  12 2467-2472
  • 31 Naccache J M. et al . Sarcoid-like pulmonary disorder in human immunodeficiency virus-infected patients receiving antiretroviral therapy.  Am J Respir Crit Care Med. 1999;  159 2009-2013
  • 32 Narita M, Ashkin D, Hollender E S, Pitchenik A E. Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS.  Am J Respir Crit Care Med. 1998;  158 157-161
  • 33 Ockenga J, Tillmann H L, Trautwein C, Stoll M, Manns M P, Schmidt R E. Hepatitis B and C in HIV infected patients. Prevalence and prognostic value.  J Hepatol. 1997;  27 18-24
  • 34 Palella F J. et al . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.  N Engl J Med. 1998;  338 853-860
  • 35 Proia L A, Ngui S L, Kaur S, Kessler H A, Trenholme G M. Reactivation of hepatitis B in patients with human immunodeficiency virus infection treated with combination antiretroviral therapy.  Am J Med. 2000;  108 249-251
  • 36 Puoti M. et al . Liver damage and kinetics of hepatitis C virus and human immunodeficiency virus replication during the early phase of combination antiretroviral treatment.  J Infect Dis. 2000;  181 2033-2036
  • 37 Race E M, Adelson-Mitty J. et al . Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease (see comments).  Lancet. 1998;  351 252-255
  • 38 Rodriguez R. et al . Opportunistic infections shortly after beginning highly active antiretroviral therapy.  Antivir Ther. 1998;  3 229-231
  • 39 Sansone G R, Frengley J D. Impact of HAART on causes of death of persons with late-stage AIDS.  J Urban Health. 2000;  77 166-175
  • 40 Schwietert M, Battegay M. Fokale mycobakterielle Lymphadenitis nach Beginn einer hochaktiven antiretroviralen Therapie.  Dtsch Med Wochenschr. 1999;  124 45-48
  • 41 Soriano V, Dona C, Rodriguez R, Barreiro P, Gonzalez L. Discontinuation of secondary prophylaxis for opportunistic infections in HIV-infected patients receiving highly active antiretroviral therapy.  AIDS. 2000;  14 383-386
  • 42 Sulkowski M S. et al . Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection.  JAMA. 2000;  283 74-80
  • 43 Vento S, Renzini C, Casali F, Ghironzi G, Concia E. Highly active antiretroviral therapy.  Lancet. 1998;  351 1058
  • 44 Weber K, Meyer D, Grosse V, Stoll M, Schmidt R E, Heiken H. Reconstitution of NK cell activity in HIV-1 infected individuals receiving antiretroviral therapy.  Immunobiology. 2000;  202 172-178
  • 45 Whitcup S M. Cytomegalovirus retinitis in the era of highly active antiretroviral therapy.  JAMA. 2000;  283 653-657
  • 46 Wolters L M, Niesters H G, de Man RA, Schalm S W. Antiviral treatment for human immunodeficiency virus patients co-infected with hepatitis B virus.  Antiviral Res. 1999;  42 71-76
  • 47 Woods M L. et al . HIV combination therapy: partial immune restitution unmasking latent cryptococcal infection.  AIDS. 1998;  12 1491-1494
  • 48 Zegans M E, Walton R C. et al . Transient vitreous inflammatory reactions associated with combination antiretroviral therapy in patients with AIDS and cytomegalovirus retinitis.  Am J Ophthalmol. 1998;  125 292-300
  • 49 Zietz C, Bogner J R, Goebel F D, Lohrs U. An unusual cluster of cases of CastlemanŽs disease during highly active antiretroviral therapy for AIDS.  N Engl J Med. 1999;  340 1923-1924
  • 50 Zylberberg H, Pialoux G. et al . Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy.  Clin Infect Dis. 1998;  27 1255-1258

Korrespondenz

PD Dr. med. Matthias Stoll

Abteilung Klinische Immunologie, Medizinische Hochschule Hannover

Carl-Neuberg-Straße 1

D-30625 Hannover

Phone: 0511/532-3637

Fax: 0511/532-5324

Email: stoll.matthias@mh-hannover.de

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