Erworbenes Immundefektsyndrom

Das erworbene Immundefektsyndrom, auch als AIDS für "Acquired Immune Deficiency Syndrome" bezeichnet, ist das Ergebnis einer chronischen Infektion mit dem Humanen Immundefizienz-Virus (HI-Virus, HIV).

Die Krankheit betrifft die folgenden Prozesse:  infektiös und hat eine Inzidenz von ca.  2 / 100.000.

Überblick

Das erworbene Immundefektsyndrom, auch als AIDS für "Acquired Immune Deficiency Syndrome" bezeichnet, ist das Ergebnis einer chronischen HIV-Infektion und konsequenter Reduktion von CD4+-Zellen. Es wird durch eine CD4+-Zellzahl <200 Zellen pro µl oder die Anwesenheit jeglicher AIDS-definierende Erkrankung unabhängig von der CD4+-Zellzahl definiert. Zu den AIDS-definierenden Erkrankungen zählen unter anderem: Kaposi-Sarkom, disseminierte oder extrapulmonale Kokzidioidomykose, Burkitt-Lymphom, Pneumocystis-Pneumonie, progressive multifokale Leukenzephalopathie, Tuberkulose und zerebrale Toxoplasmose.

Laut dem gemeinsamen Programm der Vereinten Nationen zu HIV/AIDS (UNAIDS) waren 2008 weltweit rund 33,4 Millionen Menschen (1% der erwachsenen Bevölkerung im Alter von 15-49 Jahren) mit HIV infiziert [1]. Eine HIV-Infektion wird in der Regel durch Geschlechtsverkehr, Exposition gegenüber infiziertem Blut oder durch perinatale Übertragung erworben.

Ätiologie

Eine HIV-Infektion wird durch HIV (Humanes Immundefizienz-Virus)-1 oder HIV-2 verursacht, die beide sehr ähnliche Krankheitsbilder verursachen. HIV-1 und HIV-2 gehören zu den Retroviren aus der Gattung der Lentiviren, behüllte Einzel(+)-Strang-RNA-Viren (ss(+)RNA). Die Infektion erfolgt in der Regel durch Geschlechtsverkehr, Exposition gegenüber infiziertem Blut oder durch perinatale Übertragung.

Die Anamnese sollte Risikofaktoren für die mögliche HIV-Exposition umfassen, einschließlich der folgenden:

  • Ungeschützter Geschlechtsverkehr, besonders rezeptiver Analverkehr
  • Große Anzahl an Sexualpartnern
  • Vergangene oder bestehende sexuell übertragbare Krankheiten (STDs)
  • Benutzung nicht steriler Spritzen, z.B. bei Drogenkonsum
  • Empfang von Blutprodukten (heute kaum noch von Bedeutung)
  • Schleimhautkontakt mit infiziertem Blut oder Nadelstichverletzungen
  • Mütterliche HIV-Infektion

Epidemiologie

Laut UNAIDS waren 2008 weltweit rund 33,4 Millionen Menschen (1% der erwachsenen Bevölkerung im Alter von 15-49 Jahren) mit HIV infiziert [1]. Die überwiegende Mehrheit der Infektionen wird in Afrika südlich der Sahara verzeichnet, wo geschätzt 5,2% der Bevölkerung infiziert sind. Die Anzahl der Neuinfektionen in Österreich beträgt seit 2003 etwa 450 pro Jahr [2] in Deutschland werden etwa 3000 Neuinfektionen pro Jahr berichtet.

Geschlechtsverteilung
Altersverteilung

Pathophysiologie

Die HIV-Infektion kann in folgende Stadien unterteilt werden:

  • Ansteckung und Inkubationszeit
  • Akute HIV-Infektion (auch als primäre HIV-Infektion bezeichnet)
  • Chronische HIV-Infektion: Asymptomatisch/Frühzeitige symptomatische HIV-Infektion (früher als AIDS-assoziierter Komplex bezeichnet)/AIDS, gekennzeichnet durch eine CD4-Zellzahl <200 Zellen pro µl oder die Anwesenheit von AIDS-definierenden Erkrankungen/Fortgeschrittene HIV-Infektion, charakterisiert durch eine CD4-Zellzahl <50 Zellen pro µl

Die spezifischen Details des Krankheitsprozesses, der zu AIDS führt, sind trotz umfangreicher Fortschritte in der Virologie von HIV und der Immunologie des menschlichen Wirtes nicht vollständig geklärt [3] [4]. Es kommt zu einem spezifischen Rückgang der CD4+ Helfer-T-Zellen, was zu einer Inversion des normalen CD4/CD8-T-Zell-Verhältnisses und einer Dysregulation der B-Zell-Antikörperproduktion führt [5]. Die Immunantwort auf bestimmte Antigene nimmt ab und der Wirt reagiert nicht ausreichend auf opportunistische Infektionen und normalerweise harmlose Erreger. Da hauptsächlich die zelluläre Immunität beeinflusst wird, sind die Infektionen meist fungal oder viral.

Prognose

Die Prognose bei Patienten mit unbehandelter HIV-Infektion ist schlecht, mit einer Gesamtmortalität von mehr als 90%. Sobald die Infektion zu AIDS fortgeschritten ist, ist die Überlebenszeit bei unbehandelten Patienten in der Regel weniger als 2 Jahre. Das mediane Überleben von Patienten mit fortgeschrittener HIV-Infektion (CD4-Zellzahl <50 Zellen pro µl) beträgt 12 bis 18 Monate in Abwesenheit einer antiretroviralen Therapie [6] [7] [8]. Die meisten Patienten, die an AIDS-bedingten Komplikationen versterben, haben CD4-Zellzahlen in diesem Bereich.

Symptome

AIDS manifestiert sich als rezidivierende, schwere und gelegentlich lebensbedrohliche Infektionen und/oder opportunistische Malignome. Die Symptome sind die der bestehenden Krankheit, was bedeutet, dass die HIV-Infektion als eine zugrunde liegende Ursache vermutet werden sollte, wenn ungewöhnliche Infektionen bei scheinbar gesunden Individuen auftreten.
AIDS-definierende Bedingungen sind opportunistische Erkrankungen, die aufgrund der Immunsuppression häufiger oder stärker auftreten. Dazu gehören vor allem opportunistische Infektionen, aber auch bestimmte maligne Erkrankungen. Sie wurden von den Centers for Disease Control and Prevention (CDC) und der Weltgesundheitsorganisation (WHO) definiert, wobei die Kriterien leicht variieren. Zu ihnen zählen unter anderem: Kaposi-Sarkom, disseminierte oder extrapulmonale Kokzidioidomykose, Burkitt-Lymphom, Pneumocystis-Pneumonie, progressive multifokale Leukenzephalopathie, Tuberkulose und zerebrale Toxoplasmose.

Zudem tritt eine Vielzahl von anderen Befunden durch die schwere Immunsuppression auf, darunter mukokutane Candidiasis, orale Haarleukoplakie, Herpes-Infektionen, eosinophile Follikulitis, Xerose und Prurigo nodularis. Hämatologische Aberrationen sind auch sehr häufig und Anämie, Leukopenie, Lymphopenie oder Thrombozytopenie finden sich bei über 40 Prozent der Patienten mit einer CD4+-Zellzahl <200 Zellen pro µl [9].

Diagnostik

Eine umfassende Anamnese des HIV-infizierten Patienten sollte erhoben werden. Diese umfasst eine Bewertung der Dauer und des Stadiums der HIV-Infektion, die Anwesenheit von Komorbiditäten, die die Prognose beeinflussen könnten, die Wahl der antiretroviralen Therapie und das Vorhandensein epidemiologischer Faktoren, die das Risiko der HIV-Übertragung und anderer Infektionen erhöhen. Eine umfassende körperliche Untersuchung, einschließlich Gewicht und Größe, sollte als Teil der Erstuntersuchung durchgeführt werden. Initiale Labortests sollten die Beurteilung von HIV-Staging-Parametern (CD4+-Zellzahl, HIV-RNA, HIV-Genotyp), Tests der Organfunktion und Untersuchungen auf mögliche Co-Infektionen wie Virushepatitis, Tuberkulose oder Toxoplasmose umfassen.

Therapie

Die Behandlung der HIV-Infektion hängt von dem Stadium der Erkrankung und von begleitenden opportunistischen Infektionen ab. Ab einer gewissen Zellzahl ist eine antiretrovirale Therapie, deren Ziel die Verlängerung des Lebens und die Verbesserung der Lebensqualität durch Wiederherstellung und Erhaltung der immunologischen Funktion (gemessen an CD4+-Zahlen) ist, nötig. Die Viruslast maximal und dauerhaft zu unterdrücken und die Übertragung zu verhindern sind dabei ebenfalls von großer Bedeutung [10]. Es stehen folgende Substanzgruppen zur Verfügung: Nukleosid- und Nukleotidanaloga (NRTI), Nichtnukleosidische Reverse-Transkriptase-Inhibitoren (NNRTI), HIV-Proteaseinhibitoren (PI), Entry- und Fusionsinhibitoren, sowie Integraseinhibitoren. Die Behandlung von opportunistischen Infektionen ist von größter Bedeutung und sollte auf den spezifischen Erreger gerichtet sein.

Prävention

Die wirksamsten Methoden zur Prävention der HIV-Infektion umfassen die Vermeidung von sexuellem Kontakt außerhalb einer monogamen Beziehung, sichere Sexualpraktiken für alle anderen sexuellen Begegnungen und Abstinenz von intravenösem Drogengebrauch.

Patientenhinweise

Das erworbene Immundefektsyndrom, auch als AIDS für "Acquired Immune Deficiency Syndrome" bekannt, ist das Ergebnis einer chronischen Infektion mit dem Humanen Immundefizienz-Virus (HI-Virus, HIV). Bei den Erkrankten kommt es zu lebensbedrohlichen (sogenannten opportunistischen) Infektionen und Tumoren, die sich die geschwächte Verfassung des Immunsystems zunutze machen. AIDS ist definiert als entweder eine CD4+-Zellzahl unter 200 Zellen pro μL oder das Auftreten spezifischer Erkrankungen in Verbindung mit einer HIV-Infektion. In Abwesenheit einer spezifischen Behandlung, entwickeln etwa die Hälfte der Menschen mit HIV-Infektion innerhalb von zehn Jahren AIDS. Durch die effektivere Therapie mit antiretroviralen Wirkstoffen ist AIDS in Industriestaaten seltener geworden.

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Quellen

  1. UNAIDS report on the global AIDS epidemic 2009, Available from: http://files.unaids.org/en/media/unaids/contentassets/dataimport/pub/report/2009/jc1700_epi_update_2009_en.pdf
  2. Virusepimiologische Information Nr. 03/16, Medizinische Universität Wien, Available from: http://www.virologie.meduniwien.ac.at/fileadmin/virologie/files/Epidemiologie/2016/0316.pdf
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  7. Pantaleo G, Graziosi C, Fauci AS. New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med. 1993 Feb 4;328(5):327-35.
  8. Schechter MT, Boyko WJ, Craib KJ, et al. Effects of long-term seropositivity to human immunodeficiency virus in a cohort of homosexual men. AIDS. 1987 Jul;1(2):77-82.
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