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

Tropism testing from proviral DNA – analysis of a subgroup from the Berlin Maraviroc cohort

Tropismus Testung aus proviraler DNA – Analyse einer Untergruppe der Berliner Maraviroc-Kohorte

Meeting Abstract

  • M. J. Obermeier - Medizinisches Labor Dr. Berg, Berlin, Germany
  • A. Carganico - Gemeinschaftspraxis Dupke, Baumgarten, Carganico, Berlin, Germany
  • B. Bieniek - Praxiszentrum City Ost, Berlin, Germany
  • C. Cordes - Praxiszentrum City Ost, Berlin, Germany
  • S. Dupke - Gemeinschaftspraxis Dupke, Baumgarten, Carganico, Berlin, Germany
  • K. Fischer - Gemeinschaftspraxis Dietmar Schranz und Klaus Fischer, Berlin, Germany
  • M. Freiwald - Ärztezentrum Nollendorfplatz, Berlin, Germany
  • J. Gölz - Praxiszentrum Kaiserdamm, Berlin, Germany
  • H. Hillenbrand - Praxiszentrum City Ost, Berlin, Germany
  • B. Hintsche - Gemeinschaftspraxis Hintsche Klausen, Berlin, Germany
  • G. Klausen - Gemeinschaftspraxis Hintsche Klausen, Berlin, Germany
  • S. Köppe - Gemeinschaftspraxis Köppe Kreckel, Berlin, Germany
  • P. Kreckel - Gemeinschaftspraxis Köppe Kreckel, Berlin, Germany
  • E. Lauenroth-Mai - Praxisgemeinschaft Turmstrasse, Berlin, Germany
  • C. Mayr - MVZ Ärzteforum Seestrasse, Berlin, Germany
  • A. Moll - Praxiszentrum Kaiserdamm, Berlin, Germany
  • S. Neifer - Praxis Neifer, Berlin, Germany
  • D. Prziwara - Praxisteam Mitte, Berlin, Germany
  • M. Rausch - Ärztezentrum Nollendorfplatz, Berlin, Germany
  • F. Schlote - Praxisgemeinschaft Turmstrasse, Berlin, Germany
  • C. Schuler - Praxisgemeinschaft Turmstrasse, Berlin, Germany
  • W. Schmidt - MVZ Ärzteforum Seestrasse, Berlin, Germany
  • D. Schleehauf - Praxiszentrum Kaiserdamm, Berlin, Germany
  • D. Schranz - Gemeinschaftspraxis Dietmar Schranz und Klaus Fischer, Berlin, Germany
  • T. Wünsche - Praxis Wünsche, Berlin, Germany
  • T. Berg - Medizinisches Labor Dr. Berg, Berlin, Germany
  • A. Baumgarten - Gemeinschaftspraxis Dupke, Baumgarten, Carganico, Berlin, Germany

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocHIV 07-4

DOI: 10.3205/10kit007, URN: urn:nbn:de:0183-10kit0076

Published: June 2, 2010

© 2010 Obermeier et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Background: Besides being a potent drug in treatment-experienced patients, Maraviroc (MVC) is well tolerated by most of the patients. MVC is therefore very interesting for switching strategies in case of adverse effects caused by the current, otherwise successful treatment regimen. As a CCR5-Blocker, MVC can only be part of a cART-regimen if most of the virus harboured by this patient is using CCR5 as coreceptor. Testing for CCR5 usage is not possible in these patients using phenotypic assays due to low or undetectable viral load. An option would be to perform a genotypic tropism assay using proviral DNA.

Methods: To assess the safety and assay performance we compared the results of genotypic analysis from viral RNA from 121 samples of viremic patients and the corresponding analysis from proviral DNA. Clinical performance was analysed on a subgroup of the Berlin MVC-Cohort (N=48). Genotypic analysis was performed using geno2pheno[coreceptor] with a false positive rate (FPR) setting of 20%.

Results: Of the 121 viremic patients (VL range 0.5*102 –1.6*106 cop./ml) 42 were detected CXCR4-tropic using viral RNA and 50 patients were detected CXCR4-tropic using proviral DNA. There was no correlation between height of viral load and the difference in results from proviral DNA and viral RNA. Of the 48 patients from the Berlin MVC cohort, 45 patients were detected CCR5- and 3 patients CXCR4-tropic. 68% of these patients had a viral load below detection limit of 50 cop/ml, the rest of the patients had a viral load below 200 cop/ml at baseline. 38 patients have reached an observation period of 12 weeks, with 87% of the patients now having a viral load below 50 cop./ml. 31 patients have reached an observation period of 24 weeks, with 84% of the patients having a viral load below detection limit.

Conclusions: We observe a higher rate of CXCR4 detection in proviral DNA than in viral RNA. In combination with a high FPR-cutoff of 20% reasonable safety for the patients can be realized. Patients from the Berlin MVC cohort that were switched to MVC based on proviral tropism testing showed a high rate of treatment success at weeks 12 and 24. In our opinion genotypic tropism testing from proviral DNA provides an excellent tool for switching strategies at a viral load below detection limit. Due to low patient number with a FPR below 20%, it remains unclear at the moment if lower FPR-cutoff settings than 20% are also feasible.