Neuro-AIDS in der cART-Ära

Zusammenfassung

Nach der Einführung der antiretroviralen Mehrfachkombinations-Therapien in die Behandlung der HIV-Infektion im Jahr 1996 (HAART-/cART-Ära = hochaktive antiretrovirale Therapie, combination antiretroviral therapy) erwartete man eine stetige Abnahme der Krankheitskomplikationen, insbesondere auch der Manifestationen am zentralen und peripheren Nervensystem. Bis Anfang des neuen Jahrtausends erfüllte sich diese Hoffnung; dann kam es zu einem erneuten Anstieg zunächst nur der Prävalenz, dann aber auch der Inzidenz der direkt virusassoziierten neurologischen Komplikationen bei HIV-infizierten Patienten. Die Erkrankungen, die heutzutage Neurologen im Alltag begegnen können, sind: die HIV-assoziierte Demenz (HAD) und ihre Vorstufen, die HIV-assoziierte Myelopathie, HIV-assoziierte Polyneuro- und Myopathien sowie opportunistische Infektionen und sog. Immunrekonstitutionsphänomene (IRIS). Dieser Artikel stellt praxisorientiert diagnostische Vorgehensweisen in Anlehnung an die aktuellen Leitlinien der Deutschen Gesellschaft für Neurologie und therapeutische Optionen dar.

Abstract

After the introduction of antiretroviral combination therapy for the treatment of HIV infection in 1996 (highly active antiretroviral therapy = HAART, nowadays called combination antiretroviral therapy = cART), a steady decline in infection associated complications had been expected, especially with respect to central and peripheral nervous system manifestations. Until the beginning of the new millenium this hope came in fact true, but since then there has been a slow, but constant rise in the prevalence, and later on also in the incidence of directly virus-associated neurological complications in HIV infected patients. HIV-associated diseases that neurologists might see in their routine work include HIV-associated dementia (HAD) and its precursor stages, HIV-associated myelopathy, HIV-associated polyneuropathies and myopathies as well as the opportunistic brain infections and immune reconstitution phenomena (IRIS). This article describes practical diagnostic procedures according to the guidelines of the German Neurological Society and the respective therapeutic options.

Schlüsselwörter

Neuro-AIDS - HIV-assoziierte Demenz - Immunrekonstitutionssyndrom - HIV-assoziierte Myelopathie - HIV-assoziierte Polyneuropathie

Key words

neuro-AIDS - HIV-associated dementia - immune reconstitution phenomena (IRIS) - HIV-associated myelopathy - HIV-associated polyneuropathy

• Literatur

• 1 Dore GJ, Li Y, McDonald A et al. Impact of highly active antiretroviral therapy on individual AIDS-defining illness incidence and survival in Australia. J Acquir Immune Defic Syndr 2002; 29: 388-395
• 2 Heaton RK, Franklin DR, Ellis RJ et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 2011; 17: 3-16
• 3 Hersh BP, Rajendran PR, Battinelli D. Parkinsonism as the presenting manifestation of HIV infection: improvement on HAART. Neurology 2001; 56: 278-279
• 4 Arendt G. Neurological manifestations of HIV-infection in the era of highly active antiretroviral therapy (HAART). Fortschr Neurol Psychiatr 2005; 73: 577-586
• 5 Arendt G, Nolting T, Frisch C et al. Intrathecal viral replication and cerebral deficits in different stages of human immunodeficiency virus disease. J Neurovirol 2007; 13: 225-232
• 6 Cysique LA, Maruff P, Brew BJ. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol 2004; 10: 350-357
• 7 Nath A, Schiess N, Venkatesan A et al. Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 2008; 20: 25-31
• 8 Arendt G, Nolting T. Neurological manifestations of the HIV infection. MMW Fortschr Med 2005; 147 Spec No 1: 75-77
• 9 Gibbie T, Mijch A, Ellen S et al. Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year follow-up. HIV Med 2006; 7: 112-121
• 10 Ellis RJ, Gamst AC, Capparelli E et al. Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 2000; 54: 927-936
• 11 Antinori A, Arendt G, Becker JT et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007; 69: 1789-1799
• 12 Letendre S, Marquie-Beck J, Capparelli E et al. Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008; 65: 65-70
• 13 Patel K, Ming X, Williams PL et al. Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents. AIDS 2009; 23: 1893-1901
• 14 Cysique LA, Waters EK, Brew BJ. Central Nervous System Antiretroviral Efficacy in HIV infection: A Qualitative and Quantitative Review and implications for future research. BMC Neurol 2011; 11: 148
• 15 Simioni S, Cavassini M, Annoni JM et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 2010; 24: 1243-1250
• 16 Simpson DM, Tagliatti M. Neurologic manifestations of HIV infection. Ann Intern Med 1994; 121: 769-785
• 17 Di Rocco A, Tagliati M. Remission of HIV myelopathy after highly active antiretroviral therapy. Neurology 2000; 55: 456
• 18 Di Rocco A, Werner P, Bottiglieri T et al. Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled study. Neurology 2004; 63: 1270-1275
• 19 Schifitto G, McDermott MP, McArthur JC et al. Incidence of and risk factors for HIV-associated distal sensory polyneuropathy. Neurology 2002; 58: 1764-1768
• 20 Morgello S, Estanislao L, Simpson D et al. HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank. Arch Neurol 2004; 61: 546-551
• 21 Keswani SC, Chander B, Hasan C et al. FK506 is neuroprotective in a model of antiretroviral toxic neuropathy. Ann Neurol 2003; 53: 57-64
• 22 Phillips TJ, Cherry CL, Cox S et al. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS ONE 2010; 5: e14433
• 23 Viard JP, Vittecoq D, Lacroix C et al. Response of HIV-1-associated polymyositis to intravenous immunoglobulin. Am J Med 1992; 92: 580-581
• 24 Cingolani A, De Luca A, Ammassari A et al. PCR detection of Toxoplasma gondii DNA in CSF for the differential diagnosis of AIDS-related focal brain lesions. J Med Microbiol 1996; 45: 472-476
• 25 Cultrera R, Seraceni S, Contini C. Efficacy of a novel reverse transcriptase-polymerase chain reaction (RT-PCR) for detecting Toxoplasma gondii bradyzoite gene expression in human clinical specimens. Mol Cell Probes 2002; 16: 31-39
• 26 French M, Price P. Immune restoration disease in HIV patients: aberrant immune responses after antiretroviral therapy. J HIV Ther 2002; 7: 46-51
• 27 Arendt G, von Giesen HJ. Klinik, Pathogenese und Therapie von Neuro-AIDS. Bremen: Uni-MED 2000;