Opportunistische Infektionen des Nervensystems bei AIDS

ZUSAMMENFASSUNG

Opportunistische Infektionen des ZNS sind bei Menschen mit HIV-Infektion mit einer substanziellen Morbidität und Mortalität verknüpft. Die häufigsten Infektionen sind die progressive multifokale Leukenzephalopathie (PML), die Toxoplasma-Enzephalitis und die Kryptokokken-Meningitis. Die Inzidenz liegt unter der antiretroviralen Kombinationstherapie (cART) unter 1,0/1000 Patientenjahre. Andere Infektionen wie die Cytomegalievirus-Enzephalitis, das EBV-assoziierte primäre ZNS-Lymphom, Infektionen mit Mykobakterien, anderen Herpesviren und anderen Pilzen wie Aspergillus und Candida sind mittlerweile noch seltener. Komplizierend ist das inflammatorische Immunrekonstitutionssyndrom (IRIS), welches nach Initiierung einer cART in Anwesenheit einer gleichzeitigen opportunistischen Infektion auftreten kann. Durch die moderne cART, aber auch durch andere Behandlungsmöglichkeiten ist die Prognose der opportunistischen Infektionen entscheidend verbessert worden.

ABSTRACT

Opportunistic CNS infections of HIV patients are accompanied by a substantial morbidity and mortality. Most frequent infections are progressive multifocal leukoencephalopathy (PML), Toxoplasma encephalitis and Cryptococcus meningitis. The incidence decreased under antiretroviral combination treatment (cART) below 1.0/1,000 patient years. Other infections such as Cytomegalie virus encephalitis, EBV associated primary CNS lymphoma, infections with Mykobacteria, other herpesviruses and fungi such as Aspergillus and Candida are very infrequent today. The inflammatory immune reconstitution syndrome (IRIS) complicates the disease course especially if cART has to be initiated during opportunistic CNS infections. However, modern cART dramatically improved prognosis of opportunistic CNS infections.

Schlüsselwörter

HIV-Infektion - opportunistische Infektion - PML - Toxoplasma-Enzephalitis - Kryptokokken-Meninigitis - IRIS

Key words

HIV - opportunistic infection - PML - toxoplasma encephalitis - cryptococcus meningitis - IRIS

• Literatur

• 1 Maschke M, Kastrup O, Esser S. et al Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART).. J Neurol Neurosurg Psychiatry 2000; 69: 376-80
• 2 Arendt G, Grauer O, Hahn K. et al Neues bei HIV und Neuro-Aids.. Akt Neurol 2015; 42: 445-455
• 3 Maschke M. Virale Infektionen des zentralen Nervensystems und Neuro-Aids: was ist neu?. Neuro u2d 2020; 3: 23-39
• 4 The UK Collaborative HIV Cohort (CHIC) Study Steering Committee. HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era.. Eur J Neurol 2011; 18: 527-534
• 5 Tan IL, Smith BR, von Geldern G. et al HIV-associated opportunistic infections of the CNS.. Lancet Neurol 2012; 11: 605-617
• 6 Albarillo F, O’Keefe P. Opportunistic Neurologic Infections in Patients with Acquired Immunodeficiency Syndrome (AIDS).. Curr Neurol Neurosci Rep 2016; 16: 10
• 7 Le LT, Spudich SS. HIV-associated neurologic disorders and central nervous system opportunistic infections on HIV.. Semin Neurol 2016; 36: 373-81
• 8 Bowen LN, Smith B, Reich D. et al HIV-associated opportunistic CNS infections: pathophysiology, diagnosis and treatment.. Nat Rev Neurol 2016; 12: 662-674
• 9 Happe S, Fischer A, Heese Ch. et al HIV-assoziierte cerebrale Toxoplasmosis – Review und retrospektive Analyse von 36 Patienten.. Nervenarzt 2002; 73: 1174-8
• 10 Marra CM. Central nervous system infection with Toxoplasma gondii.. Handb Clin Neurol 2018; 152: 117-122
• 11 Martin-Blondel G, Alvarez M, Delobel P. et al Toxoplasmic encephalitis IRIS in HIV-infected patients: a case series and review of the literature.. J Neurol Neurosurg Psychiatry 2011; 82: 691-3
• 12 Maschke M, Kastrup O, Forsting M. et al Update on neuroimaging in infectious central nervous system disease.. Curr Opin Neurol 2004; 17: 475-80
• 13 Offiah CE, Turnbull IW. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients.. Clin Radiol 2006; 61: 393-401
• 14 Pereira-Chioccola VL, Vidal JE. et al Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients.. Future Microbiol 2009; 4: 1363-79
• 15 Arendt G, Maschke M. HIV und AIDS: neurologische Manifestationen. In: Diener HC, Gerloff C, Dieterich M (Hrsg.). Therapie und Verlauf neurologischer Erkrankungen.. Stuttgart: Kohlhammer; 2018: 655-683
• 16 Thoden J, Potthoff A, Bogner JR. et al Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066).. Infection 2013; 41 (Suppl. 02) 91-115
• 17 Dannemann B, McCutchan JA, Israelski D. et al Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group.. Ann Intern Med 1992; 116: 33-43
• 18 Leport C, Raffi F, Matheron S. et al Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome. Efficacy of long-term continuous therapy.. Am J Med 1988; 84: 94-100
• 19 Katlama C, De Wit S, O’Doherty E. et al Pyrimethamine-clindamycin vs.pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS.. Clin Infect Dis 1996; 22: 268-275
• 20 Hernandez AV, Thota P, Pellegrino D. et al A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprimsulfamethoxazole a real option?. HIV Med 2017; 18: 115-124
• 21 Tremont-Lukats IW, Garciarena P, Juarbe R. et al The immune inflammatory reconstitution syndrome and central nervous system toxoplasmosis.. Ann Intern Med 2009; 150: 656-657
• 22 van Bilsen WPH, van den Berg CHSB, Rijnders BJA. et al Immune reconstitution inflammatory syndrome associated with toxoplasmic encephalitis in HIV-infected patients.. AIDS 2017; 31: 1415-1424
• 23 May RC, Stone NR, Wiesner DL. et al Cryptococcus: from environmental saprophyte to global pathogen.. Nat Rev Microbiol 2016; 14: 106-17
• 24 Rajasingham R, Smith RM, Park BJ. et al Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis.. Lancet Infect Dis 2017; 17: 873-881
• 25 Smith IM, Stephan C, Hogardt M. et al Cryptococcosis due to Cryptococcus gattii in Germany from 2004–2013. Int J Med Microbiol 2015; 305: 719-23
• 26 Jarvis JN, Meintjes G, Bicanic T. et al Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.. PLoS Pathog 2015; 11: e1004754
• 27 Perfect JR, Dismukes WE, Dromer F. et al Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.. Clin Infect Dis 2010; 50: 291-322
• 28 Arendt G, Eggers C. Eggers. et al Diagnostik und Therapie HIV-1-assoziierter neurologischer Erkrankungen.. AWMF-Registernummer: 030/044
• 29 Wiesner DL, Boulware DR. Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome(IRIS): Pathogenesis and Its Clinical Implications.. Curr Fungal Infect Rep 2011; 5: 252-261
• 30 Katchanov J, Branding G, Jefferys L. et al Neuroimaging of HIV-associated cryptococcal meningitis: comparison of magnetic resonance imaging findings in patients with and without immune reconstitution.. Int J STD AIDS 2016; 27: 110-7
• 31 Albrecht H, Hoffmann C, Degen O. et al Highly active antiretroviral therapy significantly improves the prognosis of patients with HIV-associated progressive multifocal leukoencephalopathy.. AIDS 1998; 12: 1149-1154
• 32 Clifford DB, Yiannoutsos C, Glicksman M. et al HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy.. Neurology 1999; 52: 623-625
• 33 Gasnault J, Costagliola D, Hendel-Chavez H. et al ANRS 125 Trial Team. Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early 5-drug combination antiretroviral therapy.. PLoS One 2011; 6: e20967
• 34 Melliez H, Mary-Krause M, Bocket L. et al French Hospital Database on HIV (ANRS-C4). Risk of Progressive Multifocal Leukoencephalopathy in the Combination Antiretroviral Therapy Era in the French Hospital Database on Human Immunodeficiency Virus (ANRS-C4).. Clin Infect Dis 2018; 67: 275-282
• 35 Happe S, Lünenborg N, Rickert CH. et al Progressive multifokale Leukoenzephalopathy bei AIDS. Übersicht und retrospektive Analyse von 17 Patienten.. Nervenarzt 2000; 71: 96-104
• 36 Kastrup O, Maschke M, Diener HC. et al Progressive multifocal leukoencephalopathy limited to the brain stem.. Neuroradiology 2002; 44: 227-9
• 37 Berger JR, Aksamit AJ, Clifford DB. et al PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section.. Neurology 2013; 80: 1430-8
• 38 Godi C, De Vita E, Tombetti E. et al High b-value diffusion-weighted imaging in progressive multifocal leukoencephalopathy in HIV patients.. Eur Radiol 2017; 27: 3593-3599
• 39 Thurnher MM, Boban J, Rieger A. et al Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor.. AJNR Am J Neuroradiol 2019; 40: 994-1000
• 40 Swinnen B, Saegeman V, Beuselinck K. et al Predictive value of JC virus PCR in cerebrospinal fluid in the diagnosis of PML.. Diagn Microbiol Infect Dis 2019; 95: 114859
• 41 Nakamichi K, Kawamoto M, Ishii J. et al Improving detection of JC virus by ultrafiltration of cerebrospinal fluid before polymerase chain reaction for the diagnosis of progressive multifocal leukoencephalopathy.. BMC Neurol 2019; 19: 252
• 42 De Luca A, Ammassari A, Pezzotti P. et al IRINA, ACTG 363 Study Groups. Cidofovir in addition to antiretroviral treatment is not effective for AIDS-associated progressive multifocal leukoencephalopathy: a multicohort analysis.. AIDS 2008; 22: 1759-67
• 43 Cortese I, Muranski P, Enose-Akahata Y. et al Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy.. N Engl J Med 2019; 380: 1597-1605
• 44 Walter O, Treiner E, Bonneville F. et al Treatment of Progressive Multifocal Leukoencephalopathy with Nivolumab.. N Engl J Med 2019; 380: 1674-1676
• 45 Steiner I, Benninger F. Maraviroc in PML-IRIS: A separate ball game under HIV infection and natalizumab?.. Neurol Neuroimmunol Neuroinflamm 2017; 4: e331
• 46 Giacomini PS, Rozenberg A, Metz I. et al Maraviroc and JC virus-associated immune reconstitution inflammatory syndrome.. N Engl J Med 2014; 370: 486-488