EucoHIV - The European coreceptor HIV-1 cohort study: outcomes of - - PowerPoint PPT Presentation

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EucoHIV - The European coreceptor HIV-1 cohort study: outcomes of maraviroc use across Europe Matthias Dring Max Planck Institute for Informatics May 2, 2016 Overview of the EucoHIV study Coreceptor usage: Follow for up to 48 weeks and

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EucoHIV - The European coreceptor HIV-1 cohort study: outcomes of maraviroc use across Europe

Matthias Döring

Max Planck Institute for Informatics May 2, 2016

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May 2, 2016 2/

Overview of the EucoHIV study

1500 HIV-1 infected patients Switch to maraviroc- containing regimen Follow for up to 48 weeks and determine outcomes Measure mostly on ART Coreceptor usage: mostly R5 Clinical covariates

Coreceptor usage
Viral load
CD4 cell counts
Drug resistance

Usually 150 mg BID

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Further objectives of EucoHIV

May 2, 2016 3/19

Enhancement of geno2pheno[coreceptor] Development of the PhyloGeoTool Quality assurance Educational activities

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Maraviroc inhibits the cell entry of R5 viruses

May 2, 2016 4/19

Delhalle et al. Phages and HIV-1: From Display to Interplay.

Int. J. Mol. Sci. 2012

Inhibited Not Inhibited Not Inhibited R5 X4-capable

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Reasons for starting/stopping maraviroc therapy

May 2, 2016 5/19

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%)

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Coreceptor usage of patients at baseline

May 2, 2016 6/19

Naive Experienced, Unknown VL VL Failure LLV Suppressed VL

87% R5 and 13% X4-capable*
Treatment-experienced: 83%
Failure: 30%
LLV: 17%
Suppressed: 25%

*15% FPR threshold from g2p or phenotypic test

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CD4 cell counts at baseline

May 2, 2016 7/19

R5

X4

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Multiple cutoffs for annotating coreceptor usage

May 2, 2016 8/19

FPR: false positive rate

Low FPRs: X4-capable

variants

High FPRs: R5 virus

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Reduction in viral loads during maraviroc therapy

May 2, 2016 9/19

Weeks after starting maraviroc therapy Log VL change

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Improvement of immunological status

May 2, 2016 10/19

Weeks after starting maraviroc therapy

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Enhancement of geno2pheno[coreceptor]

May 2, 2016 11/19

Log reduction of viral load after 8 weeks for patients with failing therapies at BL

Questions

Cutoff for the new g2p version?
New data and methods?

Good separation of R5 and X4-capable variants!

Pfeifer, N., & Lengauer, T. (2012). Improving HIV coreceptor usage prediction in the clinic using hints from next-generation sequencing

data. Bioinformatics,28(18), i589-i595.

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Current status of the PhyloGeoTool

May 2, 2016 12/19

Current version available at regatools.med.kuleuven.be/phylogeotool/PhyloGeoTool/

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Coreceptor prediction for HIV-2

May 2, 2016 13/19

Overview of results CSV output Visualization coreceptor-hiv2.geno2pheno.org

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Thanks for your attention and thanks to

May 2, 2016 14/19

The EucoHIV steering committee
Charles Boucher
Anna Maria Geretti
Rolf Kaiser
Thomas Lengauer
Anne-Mieke Vandamme
Maurizio Zazzi
ViiV Healthcare
Andrea De Luca
Nico Pfeifer
Eugen Schülter
All contributors to the HIV-2 project, particularly:
Pedro Borrego
Nuno Taveira
Achim Büch
Josef Eberle

Max Planck Institute for Informatics, Saarbrücken Nico Pfeifer University of Lisbon Pedro Borrego University of Lisbon Nuno Taveira University of Siena, Italy Andrea De Luca University Hospital Cologne Eugen Schülter

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EucoHIV criteria for patient selection

May 2, 2016 15/19