Open Access Research

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

Jan Fehr1, Tracy R Glass2, Séverine Louvel34, François Hamy3, Hans H Hirsch14, Viktor von Wyl5, Jürg Böni6, Sabine Yerly7, Philippe Bürgisser8, Matthias Cavassini9, Christoph A Fux10, Bernard Hirschel11, Pietro Vernazza12, Gladys Martinetti13, Enos Bernasconi14, Huldrych F Günthard5, Manuel Battegay1, Heiner C Bucher2, Thomas Klimkait4* and the Swiss HIV Cohort Study

Author Affiliations

1 Division of Infectious Diseases & Hospital Epidemiology, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, Switzerland

2 Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Hebelstrasse 10, CH-4031 Basel, Switzerland

3 InPheno AG, Vesalgasse 1, CH-4051 Basel, Switzerland

4 Department of Biomedicine, Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland

5 Division of Infectious Diseases & Hospital Epidemiology, University Hospital, University of Zürich, Raemistrasse 100, CH-8091 Zurich, Switzerland

6 Swiss National Centre for Retroviruses, Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

7 Laboratory of Virology, University Hospital of Geneva and University of Geneva Medical School, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva, Switzerland

8 Division of Immunology, University Hospital Lausanne, University of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland

9 Infectious Diseases Service, Department of Internal Medicine, University Hospital of Lausanne, University of Lausanne, CH-1011 Lausanne, Switzerland

10 Clinics for Infectious Diseases Bern, University Hospital and University of Bern, Freiburgstrasse 4, CH-3010 Bern, Switzerland

11 Division of Infectious Diseases, University Hospital of Geneva and University of Geneva Medical School, Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva, Switzerland

12 Division of Infectious Diseases, Cantonal Hospital St. Gallen, Rorschacher Strasse 95, CH-9007 St. Gallen, Switzerland

13 Institute for Medical Microbiology, Ospedale Civico Lugano, Via Tesserete 46, CH-6903 Lugano, Switzerland

14 Division of Infectious Diseases, Ospedale Civico Lugano, Via Tesserete 46, CH-6903 Lugano, Switzerland

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Journal of Translational Medicine 2011, 9:14  doi:10.1186/1479-5876-9-14

Published: 21 January 2011

Abstract

Background

Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients.

Methods

Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5log reduction).

Results

Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15).

Conclusions

In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.