gms | German Medical Science

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Deutsche Gesellschaft für Infektiologie,
Deutsche AIDS-Gesellschaft,
Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit,
Paul-Ehrlich-Gesellschaft für Chemotherapie

23.06. - 26.06.2010, Köln

Association of a constitutive androstane receptor polymorphism (rs2307424) with treatment discontinuation in HIV+ patients receiving efavirenz

Zusammenhang vom konstitutiven Androstane Rezeptor Polymorphismus (rs2307424) mit dem Therapieabbruch bei HIV+ Patienten, die mit Efavirenz therapiert wurden

Meeting Abstract

  • H. Hendra - Klinik I für Innere Medizin, Universität zu Köln, Germany
  • M. Platten - Klinik I für Innere Medizin, Universität zu Köln, Germany
  • C. Wyen - Klinik I für Innere Medizin, Universität zu Köln, Germany
  • H. Jäger - HIV Research and Clinical Care Centre, München, Germany
  • T. Harrer - Klinik III Innere Medizin, Universitätklinikum Erlangen, Universität Erlangen, Nürnberg, Germany
  • S. Esser - Klinik für Dermatologie, Universitätslinikum Essen, Germany
  • N. H. Brockmeyer - Klinik für Dermatologie, Krankenhaus St. Josef, Bochum, Germany
  • J. R. Bogner - Klinik für Innere Medizin, Klinikum der Universität München, Germany
  • B. Bieniek - Gemeinschaftspraxis Bieniek Cordes, Berlin, Germany
  • C. Michalik - ZKS Köln, Germany
  • D. Egan - Department of Pharmacology and Therapeutics, School of Biomedical Sciences, University of Liverpool, United Kingdom
  • G. Fätkenheuer - Klinik I für Innere Medizin, Universität zu Köln, Germany
  • D. Back - Department of Pharmacology and Therapeutics, School of Biomedical Sciences, University of Liverpool, United Kingdom
  • A. Owen - Department of Pharmacology and Therapeutics, School of Biomedical Sciences, University of Liverpool, United Kingdom
  • Deutsches Kompetenznetz HIV/AIDS

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocHIV 07-3

DOI: 10.3205/10kit006, URN: urn:nbn:de:0183-10kit0067

Veröffentlicht: 2. Juni 2010

© 2010 Hendra et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objectives: The constitutive androstane receptor (CAR) and the pregnane-X-receptor (PXR) both regulate CYP2B6 expression. CYP2B6 is primarily responsible for metabolic clearance of efavirenz (EFV) and SNPs in the CYP2B6 gene are associated with EFV pharmacokinetics. A correlation between both these nuclear receptors and CYP2B6 expression was reported in liver, in the absence of xenobiotics. Since CAR and PXR are correlated with CYP2B6 and EFV is a potent substrate for this enzyme, SNPs in CYP2B6, CAR and PXR were investigated for their association with early (<3 months) discontinuation of EFV therapy.

Methods: Patients initiating therapy with an EFV based regimen were included (80 female; 95 black). The median (range) age was 46 (26–82), viral load was <50 (<50–1x106) and CD4 count was 406.5 (0–3233). Following informed consent, DNA was extracted from whole blood and genotyping for CYP2B6 (516G>T, rs3745274), CAR (rs2307424) and PXR (44477T>C, rs1523130; 63396C>T, rs2472677; 69789A>G, rs763645) were conducted using standard methodology. Multivariate regression by backwards method was used to assess the influence of SNPs and demographics on whether patients discontinued therapy within the first 3 months.

Results: Of the 373 patients, 131 withdrew from therapy within the first 3 months. The multivariate model had an adjusted R2=0.042; F=5, p<0.001. Ethnicity (β=–0.17; P=0.002, CAR (β=–0.12; P=0.02), and possibly CYP2B6 516G>T (β=0.09; P=0.07) and PXR 63396C>T (β=0.10; P=0.07) were associated with discontinuation within three months.

Conclusion: These data indicate that genetic variability in CYP2B6, CAR and PXR contribute to early treatment discontinuation in response to EFV-based antiretroviral regimens. Furthermore, as yet uncharacterised ethnic differences are also likely to contribute.