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Hochaktive antiretrovirale Therapie bei Neuro-AIDS

Nebenwirkungen auf das Nervensystem und Interaktionen

Highly active antiretroviral therapy of neuro-AIDS

Side effects on the nervous system and interactions

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Zusammenfassung

Die hochaktive antiretrovirale Therapie (HAART) hat zu einer mittleren Überlebenszeit im AIDS-Stadium von mehr als 10 Jahren geführt. In der Zwischenzeit sind 5 Substanzgruppen bekannt, von denen die Integraseinhibitoren und die CCR5-Antagonisten zu den neuesten und modernsten Medikamenten gehören. Die lange Überlebenszeit im AIDS-Stadium führt dazu, dass Nebenwirkungen und Interaktionen von HAART mehr in den Vordergrund treten und bezüglich der differenzialdiagnostischen Auswirkungen gegenüber den Symptomen der HIV-Infektion selbst abgegrenzt werden müssen. Nebenwirkungen von HAART betreffen das zentrale und periphere Nervensystem sowie die Muskulatur, die Neurotoxizität der einzelnen Komponenten von HAART ist substanzspezifisch außerordentlich unterschiedlich. Kenntnisse der Interaktionen von Retrovirustatika mit Neuropsychopharmaka wie Antiepileptika, Antidepressiva und Analgetika sind bei der Behandlung von Patienten mit Neuro-AIDS essenziell.

Summary

Highly active antiretroviral therapy (HAART) has increased the mean survival time in the AIDS stage to sometimes more than 10 years. Five different groups of antiretroviral medications are known, of which integrase inhibitors and CCR5 antagonists represent the newest and most modern substances. The long AIDS survival time implies that side effects and interactions become relatively more important and must be differentiated from the symptoms of HIV itself. Side effects of HAART concern the central and peripheral nervous system and the muscles. The neurotoxicity of the components in HAART varies considerably and depends on the substance itself. Knowledge of side effects and interactions of HAART with antiepileptics, antidepressants, and analgetics are essential for the treatment of patients with neuro-AIDS.

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Literatur

  1. Antinori A, Arendt G, Becker JT et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

    Article  CAS  PubMed  Google Scholar 

  2. Arendt G, Nolting T, Frisch C et al (2007) Intrathecal viral replication and cerebral deficits in different stages of human immunodeficiency virus disease. J Neurovirol 13:225–232

    Article  PubMed  Google Scholar 

  3. Arendt G (2006) Affective disorders in patients with HIV infection CNS. Drugs 20:507–518

    Google Scholar 

  4. Arendt G, Eggers C, Furrer H et al (2008) Diagnostik und Therapie HIV-1-assoziierter Erkrankungen. In: Diener HC, Putzki N (Hrsg) Leitlinien für Diagnostik und Therapie in der Neurologie. Thieme, Stuttgart, S 459–468

  5. Authier FJ, Chariot P, Gherardi RK (2005) Skeletal muscle involvement in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART). Muscle Nerve 32:247–260

    Article  PubMed  Google Scholar 

  6. Benhammou V, Tardieu M, Warszawski J et al (2007) Clinical mitochondrial dysfunction in uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues. Environ Mol Mutagen 48:173–178

    Article  CAS  PubMed  Google Scholar 

  7. Biehl K, Hudelmeier B, Reichelt D et al (2009) Abnahme der Kognition unter ddC, ddI und d4T als Komponente von HAART (Abstract). Aktuelle Neurol (im Druck)

  8. Boly L, Cafaro V, Dyner T (2006) Depressive symptoms predict increased incidence of neuropsychiatric side effects in patients treated with efavirenz. J Acquir Immune Defic Syndr 42:514–515

    Article  PubMed  Google Scholar 

  9. Cherry CL, Skolasky RL, Lal L et al (2006) Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort. Neurology 66:867–873

    Article  CAS  PubMed  Google Scholar 

  10. Cote H, Brumme ZL, Craib K et al (2002) Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. N Engl J Med 346:811–820

    Article  CAS  PubMed  Google Scholar 

  11. Cupler EJ, Danon MJ, Jay C et al (1995) Early features of AZTe-associated myopathy: Histopathological findings and clinical correlations. Acta Neuropathol (Berl) 90:1–6

    Google Scholar 

  12. Deutsche Neuro-AIDS-Arbeitsgemeinschaft DNAA (2000) Erkrankungen des peripheren Nervensystems und der Muskulatur bei der HIV-Infektion. Nervenarzt 71:442–450

    Article  Google Scholar 

  13. Dorey-Stein Z, Amorosa VK, Kostman JR et al (2008) Severe weight gain, lipodystrophy, dyslipidemia and obstructive sleep apnea in a human immunodeficiency virus-infected patient following highly active antiretroviral therapy. J Cardiometab Syndr 3:111–114

    Article  PubMed  Google Scholar 

  14. Evers S, Wibbeke B, Reichelt D et al (2000) The impact of HIV infection on primary headache. Unexpected findings from retrospective, cross-sectional and prospective analyses. Pain 85:191–200

    Article  CAS  PubMed  Google Scholar 

  15. Evers S, Husstedt IW (2009) Kopfschmerzen während der HIV-Infektion. Nervenarzt (im Druck)

  16. Gray F, Chrétien F, Vallat-Decouvelaere AV, Scaravilli F (2003) The changing pattern of HIV neuropathology in the HAART era. J Neuropathol Exp Neurol 62:429–440

    PubMed  Google Scholar 

  17. Gutierrez F, Navarro A, Padilla S et al (2005) Prediction of neuropsychiatric adverse events associated with long-term efavirenz therapy, using plasma drug level monitoring. Clin Infect Dis 41:1648–1653

    Article  CAS  PubMed  Google Scholar 

  18. Hahn K, Arendt G, Braun JS, German Neuro-AIDS Working Group (2004) A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies. J Neurol 251:1260–1266

    Article  CAS  PubMed  Google Scholar 

  19. Harry TC, Matthews M, Salvary I (2000) Indinavir use: Associated reversible hair loss and mood disturbance. Int J STD AIDS 11:474–476

    Article  CAS  PubMed  Google Scholar 

  20. Hawkins T, Geist C, Young B et al (2005) Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients. HIV Clin Trials 6:187–196

    Article  PubMed  Google Scholar 

  21. HIV Neuromuscular Syndrome Study Group (2004) HIV-associated neuromuscular weakness syndrome. AIDS 18:1403–1412

    Article  Google Scholar 

  22. Jellinger KA, Setinek U, Drlicek M et al (2000) Neuropathology and general autopsy findings in AIDS during the last 15 years. Acta Neuropathol (Berl) 100:213–220

    Google Scholar 

  23. Johnson AA, Ray AS, Hanes J et al (2001) Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase. J Biol Chem 276:40847–40857

    Article  CAS  PubMed  Google Scholar 

  24. Keilbaugh SA, Prusoff WH, Simpson MV (1991) The PC12 cell as a model for studies of the mechanism of induction of peripheral neuropathy by anti-HIV-1 dideoxynucleoside. Biochem Pharmacol 42:5–8

    Article  Google Scholar 

  25. Kellinghaus C, Engbring C, Kovac S et al (2008) Frequency of seizures and epilepsy in neurological HIV-infected patients. Seizure 17:27–33

    Article  CAS  PubMed  Google Scholar 

  26. Lafeuillade A (2001) Factors affecting adherence and convenience in antiretroviral therapy. Int J STD AIDS 12:18–24

    Article  PubMed  Google Scholar 

  27. Lee H, Hanes J, Johnson KA (2003) Toxicity of nucleoside analogues used to treat AIDS and the selectivity of the mitochondrial DNA polymerase. Biochemistry 42:14711–14719

    Article  CAS  PubMed  Google Scholar 

  28. Lewis W, Kohler JJ, Hosseini SH et al (2006) Antiretroviral nucleosides, deoxynucleotide carrier and mitochondrial DNA: Evidence supporting the DNA pol γ hypothesis. AIDS 20:675–684

    Article  CAS  PubMed  Google Scholar 

  29. Martin AM, Hammond E, Nolan D et al (2003) Accumulation of mitochondrial DNA mutations in human immunodeficiency virus-infected patients treated with nucleoside analogue reverse-transcriptase inhibitors. Am J Hum Genet 72:549–560

    Article  CAS  PubMed  Google Scholar 

  30. McArthur J, Brew BJ, Nath Avi (2005) Neurological complications of HIV infection. Lancet Neurol 4:543–555

    Article  PubMed  Google Scholar 

  31. McArthur JC, Haughey N, Gartner S et al (2003) Human immunodeficiency virus-associated dementia: An evolving disease. J Neurovirol 9:205–221

    Article  CAS  PubMed  Google Scholar 

  32. Mc Mahon DK, Dinubile MJ, Meibohm AR et al (2007) For the protokol 060 study group.efficacy, safety and tolerabilty of long-term combination antiretroviral therapy in asymptomatic treatment adults with early HIV-infection. HIV Clin Trials 8:269–281

    Article  Google Scholar 

  33. Medina DJ, Tsai CH, Hsiung GD, Cheng YC (1994) Comparison and mitochondrial morphology, mitochondrial DNA content and celle viability in cultured cells treated with three anti-human immunodeficiency virus dideoxynucleosides. Antimicrob Agents Chemother 46:1824–1828

    Google Scholar 

  34. Meemken L, Plettenberg A (2006) Psychopharmaka und HAART: interaktionen. In: Jäger H, Hoffmann C (Hrsg) HIV/AIDS Wunschwelt Heilung. Evidenz für Fortschritt oder Stillstand. Mic Landsberg, Lech, 175–177

  35. Monforte A, Lepri AC, Rezza G et al (2000) Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. AIDS 14:499–507

    Article  Google Scholar 

  36. No authors listed (2002) Depression is common among AIDS patients. Psych consult often is necessary. AIDS Alert 17:153–154

    Google Scholar 

  37. Nolan D, Mallal S (2004) Complications associated with NRTI therapy: Update on clinical features and possible pathogenic mechanisms. Antivir Ther 9:849–863

    CAS  PubMed  Google Scholar 

  38. Perkins D, Evans DL (1991) HIV-related major depression: Response to AZTe treatment. Psychosomatics 32:451–454

    CAS  PubMed  Google Scholar 

  39. Peters BS, Winer J, Landon DN et al (1993) Mitochondrial myopathy associated with chronic AZTe therapy in AIDS. Q J Med 86:5–15

    CAS  PubMed  Google Scholar 

  40. Pettersen JA, Jones G, Worthington C et al (2006) Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients: Protease inhibitor-mediated neurotoxicity. Ann Neurol 59:816–824

    Article  CAS  PubMed  Google Scholar 

  41. Poirier MC, Divi RL, Al Harthi L (2003) Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers. J Acquir Immune Defic Syndr 33:175–183

    Article  PubMed  Google Scholar 

  42. Portsmouth S, Imami N, Pires A et al (2004) Treatment of primary HIV-1 infection with nonnucleoside reverse transcriptase inhibitor-based therapy is effective and well tolerated. HIV Med 5:26–29

    Article  CAS  PubMed  Google Scholar 

  43. Proctor VE, Tesfa A, Tompkins DC (1999) Barriers to adherence to highly active antiretroviral therapy as expressed by people living with HIV/AIDS. AIDS Patient Care STDS 13:535–544

    Article  CAS  PubMed  Google Scholar 

  44. Romanelli F, Ryan M (2002) Seizures in HIV-seopositive individuals: Epidemiology and treatment. CNS Drugs 16:91–98

    Article  CAS  PubMed  Google Scholar 

  45. Schweinsburg BC, Taylor MJ, Alhassoon OM and the HNRC Group et al (2005) Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol 11:356–364

    Article  CAS  PubMed  Google Scholar 

  46. Simpson D, Estanislao L, Evans S et al (2004) HIV-associated neuromuscular weakness syndrome. AIDS 18:1403–1412

    Article  Google Scholar 

  47. Simpson DM, Kitch D, Evans SR et al (2006) HIV neuropathy natural history cohort study: Assessment measures and risk factors. Neurology 66:1679–1687

    Article  CAS  PubMed  Google Scholar 

  48. Tagliati M, Grinnell J, Godbold J, Simpson DM (1999) Peripheral nerve function in HIV infection: Clinical, electrophysiologic and laboratory findings. Arch Neurol 56:84–89

    Article  CAS  PubMed  Google Scholar 

  49. Venhoff N, Walker UA (2006) Mitochondrial disease in the offspring as a result of antiretroviral therapy. Expert Opin Drug Saf 5:373–381

    Article  CAS  PubMed  Google Scholar 

  50. Von Einsiedel RW, Berger T, Weisbrod M et al (2001) HIV-Patienten mit psychiatrischen Krankheiten. Behandlungsstrategien und Medikamenteninteraktionen. Nervenarzt 72:204–215

    Article  Google Scholar 

  51. Wise ME, Mistry K, Reid S (2002) Drug points: Neuropsychiatric complications of nevirapine treatment. BMJ 324:879

    Article  PubMed  Google Scholar 

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Husstedt: Advisory Board der Fa. Boehringer, BMS; Referentenhonorare von Astra, Boehringer, BMS, GSK, Gilead, Pfizer, Grünenthal, MSD, Behring, Forschungsförderung von Gilead für Investigator initiated study. Reichelt: Referentenhonorare von Boehringer, GSK, Gilead, Roche. Hahn: Referentenhonorare von Glaxo, Pfizer, Novartis, Serono. Arendt: Referentenhonorare von GSK, Gilead, Roche; Forschungsförderung von Gilead für Investigator initiated study. Evers: Grants und Referentenhonorare Allergan, Berlin Chemie, Boehringer, Desitin, Dysport, Eisai, GSK, MSD, Novartis, Pfizer, UCB, Weber & Webwer.

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Authors and Affiliations

  1. Klinik und Poliklinik für Neurologie, Neuro-Aids-Ambulanz, Universitätsklinikum, Albert-Schweitzer-Straße 33, 48129, Münster, Deutschland

    I.W. Husstedt & S. Evers

  2. Klinik und Poliklinik für Innere Medizin D, Universitätsklinikum, Münster, Deutschland

    D. Reichelt

  3. Institut für Neuropathologie, Universitätsklinikum, Düsseldorf, Deutschland

    E. Neuen-Jakob

  4. Neurologische Klinik, Charité Berlin, Berlin, Deutschland

    K. Hahn

  5. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum, Münster, Deutschland

    F. Kästner

  6. Psychiatrische Abteilung, Asklepios-Klinik, Langen, Deutschland

    R. von Einsiedel

  7. Die Werkstatt, Berlin, Deutschland

    B. Vielhaber

  8. Klinik für Neurologie, Universitätsklinikum, Düsseldorf, Deutschland

    G. Arendt

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  1. I.W. Husstedt
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Correspondence to I.W. Husstedt.

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Husstedt, I., Reichelt, D., Neuen-Jakob, E. et al. Hochaktive antiretrovirale Therapie bei Neuro-AIDS. Nervenarzt 80, 1133–1142 (2009). https://doi.org/10.1007/s00115-009-2684-6

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