EucoHIV - The European coreceptor HIV-1 cohort study: outcomes of maraviroc use across Europe Matthias Döring Max Planck Institute for Informatics May 2, 2016
Overview of the EucoHIV study Coreceptor usage: Follow for up to 48 weeks and mostly R5 determine outcomes Clinical covariates • Coreceptor usage • Viral load Measure • CD4 cell counts • Drug resistance 1500 HIV-1 infected patients Switch to maraviroc- mostly on ART containing regimen Usually 150 mg BID May 2, 2016 2/
Further objectives of EucoHIV Development of the PhyloGeoTool Enhancement of geno2pheno[coreceptor] Quality assurance Educational activities May 2, 2016 3/19
Maraviroc inhibits the cell entry of R5 viruses X4-capable R5 Inhibited Not Inhibited Not Inhibited Delhalle et al. Phages and HIV-1: From Display to Interplay. Int. J. Mol. Sci . 2012 May 2, 2016 4/19
Reasons for starting/stopping maraviroc therapy Reasons for starting maraviroc therapy Patients with suppressed VL: • Toxicity (TDF/EFV) • Switch due to low CD4 cell counts Patients with VL failure: • Maraviroc (150 BID) + PI Reasons for discontinuing maraviroc therapy 16.4% discontinued treatment: • Lack of response (26%) • Toxicity (12%) May 2, 2016 5/19
Coreceptor usage of patients at baseline • 87% R5 and 13% X4-capable* • Treatment-experienced: 83% • Failure: 30% • LLV: 17% • Suppressed: 25% Naive Suppressed VL VL Failure Experienced, LLV *15% FPR threshold from g2p or phenotypic test Unknown VL May 2, 2016 6/19
CD4 cell counts at baseline R5 X4 May 2, 2016 7/19
Multiple cutoffs for annotating coreceptor usage FPR: false positive rate • Low FPRs: X4-capable variants • High FPRs: R5 virus May 2, 2016 8/19
Reduction in viral loads during maraviroc therapy Log VL change Weeks after starting maraviroc therapy May 2, 2016 9/19
Improvement of immunological status Weeks after starting maraviroc therapy May 2, 2016 10/19
Enhancement of geno2pheno[coreceptor] Good separation of R5 and X4-capable variants! Questions • Cutoff for the new g2p version? • New data and methods? Log reduction of viral load after 8 weeks Pfeifer, N., & Lengauer, T. (2012). Improving HIV coreceptor usage prediction in the clinic using hints from next-generation sequencing for patients with failing therapies at BL data. Bioinformatics , 28 (18), i589-i595. May 2, 2016 11/19
Current status of the PhyloGeoTool Current version available at regatools.med.kuleuven.be/phylogeotool/PhyloGeoTool/ May 2, 2016 12/19
Coreceptor prediction for HIV-2 Overview of results coreceptor-hiv2.geno2pheno.org CSV output Visualization May 2, 2016 13/19
Thanks for your attention and thanks to Eugen Schülter Nico Pfeifer Andrea De Luca • Nico Pfeifer • Eugen Schülter • The EucoHIV steering committee Max Planck Institute • Charles Boucher University Hospital for Informatics, University of Siena, Cologne • Anna Maria Geretti Saarbrücken Italy • Rolf Kaiser • Thomas Lengauer • Anne-Mieke Vandamme • Maurizio Zazzi • ViiV Healthcare • Andrea De Luca • All contributors to the HIV-2 project, particularly: • Pedro Borrego Nuno Taveira Pedro Borrego • Nuno Taveira • Achim Büch • Josef Eberle University of Lisbon University of Lisbon May 2, 2016 14/19
EucoHIV criteria for patient selection May 2, 2016 15/19
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